Research progress on the chemical components and pharmacological effects of Physalis alkekengi L. var. franchetii (Mast.) Makino

Abstract

Physalis Calyx seu Fructus is the dry calyx or the calyx with fruit of the Solanaceae plant Physalis alkekengi L. var. franchetii (Mast.) Makino, with a long history of use in medicine and food. However, despite its many potential therapeutic and culinary applications, P. alkekengi is not being exploited for these applications on a large scale. This study analysed various research related to the different chemical components of P. alkekengi, including steroids, flavonoids, alkaloids, phenylpropanoids, sucrose esters, piperazines, volatile oils, polysaccharides, amino acids, and trace elements. In addition, research related to the pharmacological activities of P. alkekengi, including its anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, anti-tumour, and immunomodulatory effects were investigated. Research articles from 1974 to 2023 were obtained from websites such as Google Scholar, Baidu Scholar, and China National Knowledge Infrastructure, and journal databases such as Scopus and PubMed, with the keywords such as Physalis alkekengi, components, effects, and activities. This study aims to provide a comprehensive understanding of the progress of phytochemical and pharmacological research on the phytochemical and pharmacological aspects of P. alkekengi and a reference for the better exploitation of P. alkekengi in the food and pharmaceutical industries.

Graphical abstract

1. Introduction

Physalis Calyx seu Fructus, also known as Jin-Deng-Long, is the dried calyx or calyx with fruit of Physalis alkekengi L. var. franchetii (Mast.) Makino, which is a perennial herb in the Solanaceae family. It is widely distributed in Europe and Asia, including Korea and Japan, and is also cultivated in North America. In China, it is cultivated mainly in the northeast, northwest, and Inner Mongolia, with more widespread cultivation and wild growth in the northeast [1,2].

Physalis alkekengi has been used in medicine for nearly two thousand years and has been recorded in many herbal books throughout the ages, with a wide range of functions and applications. It was first recorded in Erya [3], one of the earliest dictionaries in China, and was annotated by Guo Pu. The earliest publication on traditional Chinese medicine, Shen Nong Ben Cao Jing [4] of the Han Dynasty, records that P. alkekengi has flat nature and sour flavour, and is used to treat fever and fullness, calm the mind and invigorate the vital energy, facilitate the flow of water, and alleviate pain during childbirth. Li Shizhen of the Ming dynasty recorded in Compendium of Materia Medica [5] that its seedlings, leaves, roots, and stems have bitter flavour and cold nature, and are non-toxic, and are used to relieve heat and fullness, calm the mind, improve vitality, and aid diuresis. According to Shen Nong Ben Cao Jing, the juice of P. alkekengi is effective in treating jaundice. Additionally, P. alkekengi has been used to treat sore throat, hoarse voice, cough with phlegm, aspergillosis, and eczema [6].

At present, more than 530 compounds have been isolated from P. alkekengi, mainly including steroids, flavonoids, alkaloids, phenylpropanoids, sucrose esters, piperazines, volatile oils, polysaccharides, various amino acids, and trace elements [[7], [8], [9], [10]]. Modern pharmacological studies have shown that P. alkekengi has anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, anti-tumour, and immune regulating effects and is of great nutritional and medicinal value. However, despite its many potential therapeutic and culinary applications, P. alkekengi is not being exploited for these applications on a large scale. In order to further exploit and utilize this natural resource, data relating to the chemical composition and pharmacological research of P. alkekengi from 1974 to 2023 were obtained using websites, such as Google Scholar, Baidu Scholar, and China National Knowledge Infrastructure, and journal databases, such as Scopus and PubMed, with the keywords such as Physalis alkekengi, components, effects, and activities, in an attempt to comprehensively review the chemical composition and pharmacological research progress of P. alkekengi.

2. Botanical origin

A botanical map of P. alkekengi L. var. franchetii (Mast.) Makino and pictures of dried calyxes and fruits are shown in Fig. 1(a–d). The stems are sparsely branched or unbranched, and the nodes are sometimes dilated and often pubescent, especially the younger parts. The leaves vary in shape from long-ovate to broadly ovate and sometimes rhombic-ovate, are between 5 and 15 cm long and 2–8 cm wide, apically acuminate, and have bases that are asymmetrically and narrowly cuneate. Their margins are either complete and undulate or are coarsely toothed, and both surfaces are pilose, with greater density along the nerves. Petioles are between 1 and 3 cm long. Pedicels are between 0.6 and 1.6 cm long, erect when flowering, but curve downwards in maturity, and are densely pilose but not deciduous. Calyxes are broadly campanulate, approximately 0.6 cm in length, densely pilose, with triangular teeth and hirsute margins. It has a white, rotate corolla, between 1.5 and 2 cm in diameter, with broad and short lobes spreading apically, which abruptly narrows into a triangular spike; the exterior is pubescent, and the margin is ciliate. The stamens and style are both shorter than the corolla. The fruiting pedicel is 2–3 cm long and persistently pilose. The fruiting calyx is ovate, 2.5–4 cm long and 2–3.5 cm wide, thinly leathery, and conspicuously reticulate, with 10 longitudinal ribs. It is orange or fiery red in colour, persistently pilose, apically closed, and the base is depressed. The soft, juicy berries are globose, orange-red in colour, and 1–1.5 cm in diameter. Finally, the seeds are reniform, yellowish in colour, and approximately 0.2 cm in length [2,11,12].

Fig. 1.

Images of P. alkekengi. (a) The whole plant; (b) Dried calyxes with fruits; (c) Dried calyxes; (d) Dried fruits.

3. Chemical components

Among the 530 chemical constituents isolated from P. alkekengi, steroids and flavonoids are the main active ingredients. The composition percentages of each compound type in P. alkekengi are shown in Fig. 2, and the compound information is summarised in Table 1.

Fig. 2.

Proportion of compound types isolated from P. alkekengi.

Table 1.

Compounds in Physalis alkekengi.

NO.	Compound	Molecular Formula	Origin Parts	Reference
Steroids
1	Physalin A	C28H30O10	Stems, Leaves	[7,8,10,15,32]
2	Physalin B	C28H30O9	Stems, Leaves	[7,8,10,15,32]
3	Physalin C	C28H30O9	Calyxes	[7,8,10,33]
4	Physalin D	C28H32O11	Fruits	[7,8,10,34]
5	Physalin D1	C28H32O11	Fruits	[35]
6	Physalin E	C28H32O11	Calyxes	[7,10,36]
7	Physalin F	C28H30O10	Calyxes	[7,10,26,37]
8	Physalin G	C28H30O10	Calyxes	[7,8,10,26]
9	Physalin H	C28H31ClO10	Calyxes	[7,10,26]
10	Physalin I	C29H34O11	Whole plants	[7,10,38]
11	Physalin J	C28H32O11	Stems, Leaves	[7,10,15]
12	Physalin J1	C28H32O11	Stems, Leaves	[15]
13	Physalin K	C28H30O11	Leaves	[8,10]
14	Physalin L	C28H32O10	Whole plants	[7,8,10,39]
15	Physalin M	C28H32O9	Whole plants	[7,8,10,39]
16	Physalin N	C28H30O10	Fruits, Calyxes	[7,8,10,40]
17	Physalin O	C28H32O10	Fruits, Calyxes	[7,8,10,40]
18	Physalin P	C28H30O10	Fruits	[41]
19	Physalin Q	C28H30O12	Leaves	[7]
20	Physalin QQ	C29H34O10	Roots, Stems	[42]
21	Physalin R	C28H30O9	Epigeal parts	[7,8,10,32]
22	Physalin S	C28H32O10	Epigeal parts	[7,8,10]
23	Physalin T	C28H34O11	Calyxes	[7,8,43]
24	Physalin U	C29H34O11	Whole plants	[7]
25	Physalin V	C30H34O10	Whole plants	[7]
26	Physalin W	C30H36O11	Whole plants	[7,8,38]
27	Physalin W′	C28H30O10	Aerial parts	[7,8]
28	Physalin X	C28H30O10	Roots, Stems	[7,8,42]
29	Physalin X′	C28H30O10	Calyxes	[33]
30	Physalin Y	C28H32O10	Calyxes	[7,33]
31	Physalin Z	C28H30O10	Calyxes	[7,33]
32	Physalin Ⅰ	C29H34O10	Calyxes	[7,33]
33	Physalin Ⅱ	C29H34O10	Calyxes	[7,33]
34	Physalin III	C28H32O12	Calyxes	[44]
35	Physalin IV	C28H32O12	Calyxes	[44]
36	Physalin V	C28H32O10	Calyxes	[45]
37	Physalin VI	C28H32O11	Calyxes	[45]
38	Physalin VII	C29H34O11	Calyxes	[45]
39	Physalin XIII	C29H32O11	Whole plants	[46]
40	Isophysalin I	C29H34O11	Calyxes	[45]
41	Isophysalin A	C28H29O10	Calyxes	[45]
42	Isophysalin B	C28H30O9	Stems, Leaves	[7,8,15,42]
43	Isophysalin G	C28H30O10	Calyxes	[7,8,47]
44	Alkekengilin A	C28H28O9	Calyxes	[7,8,48]
45	Alkekengilin B	C28H28O9	Calyxes	[7,8,48]
46	2,3,25,27-Tetrahydrophysalin A	C28H34O10	Calyxes	[33]
47	3-Hydroxyphysalin A	C28H32O11	Calyxes	[33]
48	3-Methoxyphysalin A	C29H34O11	Calyxes	[33]
49	3-Methoxy-7-hydroxy-6-deoxyphysalin D	C29H36O12	Calyxes	[33]
50	3-Methoxy-6,7,9,10-tetradehydrophysalin B	C29H32O10	Calyxes	[33]
51	3-O-Methylphysalin X	C29H32O10	Calyxes	[44]
52	3β-Hydroxy-2-hydrophysalin A	C28H32O11	Calyxes	[7,49]
53	3β-ethoxyl-2,3-dihydro-4,7-didehydrophysalin B	C30H34O10	Calyxes, Fruits	[50]
54	7α-Hydroxy-5-deoxy-4-dehydrophysalin IX	C28H30O11	Fruits, Calyxes	[51]
55	7β-Hydroxyphysalin A	C28H30O10	Fruits, Calyxes	[33,40]
56	7β-Hydroxyphysalin L	C28H32O10	Calyxes	[26,33,41]
57	7β-Hydroxy-25,27-didehydrophysalin L	C28H30O10	Calyxes	[33]
58	7β-Hydroxyphysalin O	C28H32O10	Calyxes	[33]
59	7β-Methoxylisophysalin B	C29H32O10	Calyxes	[45]
60	7β-Methoxylisophysalin C	C29H32O10	Calyxes	[45]
61	7β-Ethoxyl-isophysalin C	C30H34O10	Calyxes, Fruits	[50]
62	4,7-Dehydrophysalin B	C28H29O9	Calyxes	[45]
63	4,7-Didehydrophysalin B	C28H28O9	Calyxes, Roots, Stems	[33,36,41,42]
64	4,7-Didehydroneophysalin B	C28H28O9	Calyxes, Fruits	[41]
65	4,7-Didehydro-7-deoxyphysalin A	C28H28O9	Calyxes	[33]
66	4,7-Didehydro-7-deoxyneophysalin A	C28H28O9	Calyxes	[26,33]
67	4,7-Didehydro-7-deoxyneophysalin L	C28H30O9	Calyxes	[7]
68	4-Hydroxy-25,27-dihydroneophysalin A	C28H32O11	Calyxes	[33]
69	25,27-Didehydrophysalin L	C28H30O10	Calyxes	[26,52]
70	25,27-Dihydro-4,7-didehydro-7-dehydroneophysalin A	C28H30O9	Calyxes	[7,8,10]
71	25,27-Dihydro-4,7-didehydro-7-deoxyphysalin A	C28H30O9	Calyxes	[33]
72	25,27-Dihydro-4,7-didehydro-7-deoxyneophysalin A	C28H30O9	Calyxes	[7,30,36]
73	3α-Methoxy-2,3-dihydro-4,7-didehydrophysalin B	C29H32O10	Stems, Leaves	[53]
74	3β-Methoxy-2,3-dihydro-4,7-didehydrophysalin B	C29H32O10	Stems, Leaves	[53]
75	5,6α-Epoxy-physalin C	C28H30O10	Calyxes	[33]
76	5,6β-Epoxy-physalin C	C28H30O10	Calyxes	[33]
77	5-Deoxy-4-dehydrophysalin IX	C28H30O10	Fruits, Calyxes	[51]
78	5α-Ethoxy-6β- hydroxy-5,6-dihydrophysalin B	C30H36O11	Calyxes, Fruits	[54]
79	5α-hydroxy-7-dehydro-25,27-dihydro-7-deoxyneophysalin A	C28H32O10	Calyxes	[49]
80	5α-Hydroxy-25,27-dihydro-4,7-didehydro-7-deoxyneophysalin A	C28H32O10	Calyxes	[30,55]
81	5α-Hydroxy-25,27-dihydro-7-dehydro-7-deoxyneophysalin A	C28H32O10	Fruits, Calyxes	[56]
82	5α,7α-Dihydroxy-25,27-dihydrophysalin A	C28H34O11	Calyxes	[33]
83	5α,7β-Dihydroxy-25,27-dihydrophysalin A	C28H34O11	Calyxes	[33]
84	5α,6β-dihydroxy-25,27-dihydro-7-deoxyphysalin A	C28H34O11	Calyxes	[49]
85	5α,6β-Dihydroxyphysalin C	C28H32O11	Fruits	[29]
86	5α,6β-Dihydroxyphysalin R	C28H32O11	Calyxes	[7,49]
87	5β,6β-Dihydroxyphysalin D	C28H32O11	Calyxes	[33]
88	6-Hydroxy-4,5-didehydro-7-deoxyphysalin A	C28H30O10	Calyxes	[33]
89	6-Hydroxy-25,27-dihydro-4,5-didehydro-7-deoxyphysalin A	C28H32O10	Calyxes	[33]
90	16,24-cyclo-13,14-secoergosta-2-ene-18,26-dioic acid-14:17,14:27-diepoxy-11β,13,20,22-tetrahydroxy-5α-methoxy-1,15-dioxo-γ-lactone-δ-lactone	C28H30O12	Calyxes	[45]
91	Physagulin A	C30H38O7	Whole plants	[7,10]
92	Physagulin B	C30H39ClO7	Whole plants	[7,10,38]
93	Physagulin D	C34H52O10	Whole plants	[7,10]
94	Physagulin J	C30H42O8	Whole plants	[38]
95	Withaphysalin B	C28H36O6	Calyxes	[57]
96	Withaphysalin E	C28H34O7	Calyxes	[7,10]
97	Withaphysalin F	C28H36O7	Calyxes	[7,10]
98	Withaphysalin G	C28H36O6	Calyxes	[7,10]
99	Withaphysalin N	C28H36O7	Calyxes	[57]
100	Withaphysalin U	C30H41ClO7	Calyxes	[57]
101	Withagulatin A	C28H38O6	Roots, Stems	[42]
102	Withanolide A	C28H38O6	Roots, Stems	[7,58]
103	Withangulatin A	C30H38O8	Whole plants	[38]
104	Withaminimin	C30H40O8	Whole plants	[38]
105	Withalkekengin	C30H41ClO7	Whole plants	[38]
106	Physapubescin	C30H42O8	Stems, Leaves	[15]
107	Physapubescin G	C30H42O8	Stems, Leaves	[15]
108	Physapubescin I	C32H44O10	Stems, Leaves	[15]
109	Physapubescin K	C31H44O8	Stems, Leaves	[15]
110	Physapubescin M	C27H38O7	Stems, Leaves	[15]
111	Physapubescin N	C28H42O8	Stems, Leaves	[15]
112	Alkekenginin A	C30H42O8	Fruits	[35]
113	Alkekenginin B	C33H54O9	Fruits	[35]
114	Alkekenginin C	C32H46O11	Stems, Leaves	[15]
115	Alkekenginin D	C31H46O9	Stems, Leaves	[15]
116	Alkekenginin E	C30H44O9	Stems, Leaves	[15]
117	Alkekenginin F	C31H46O9	Stems, Leaves	[15]
118	26-carbonyl-physapubescin A	C30H48O8	Stems, Leaves	[15]
119	26-ethoxy-physapubescin B	C32H46O8	Stems, Leaves	[15]
120	5-hydroxyl-6-chloro-physapubescin B	C30H43ClO8	Stems, Leaves	[15]
121	Philadelphicalactone A	C28H40O7	Fruits	[59]
122	15-hydroxy-withaphysalin B	C28H36O7	Calyxes	[57]
123	15-hydroxy-withphysalin U	C28H34O6	Calyxes	[57]
124	(17S,20R,22R)-5β,6β-epoxy-18,20-dihydroxy-1-oxowitha-2,24-dienolide	C28H38O6	Calyxes	[57]
125	(17S, 20R,22R)-5β,6β:18,20-diepoxy-15α,18β-dihydroxy-1-oxowitha-24-enolide (18R and 18S)	C28H38O7	Calyxes	[57]
126	(17S,20R,22R)-5β,6β:18,20-diepoxy-18β-hydroxy-1-oxowitha-24-enolide (18R and 18S)	C28H38O6	Calyxes	[57]
127	(20S.22R)-15α-acetoxy-5α-chloro-6β,14β-dihydroxy-1-oxowitha-2,24-dienolide	C30H41ClO7	Whole plants	[60]
128	(22R)-5β,6β:14α,17:14β,26-triepoxy-2α-ethoxy-13,20,22-trihydroxy-1,15-dioxo-16α,24-cyclo-13,14-secoergosta-18,27-dioic acid 18 → 20,27 → 22-dilactone	C30H36O11	Whole plants	[60]
129	23-hydroxy-jitosapogenin-3-O-β-d-glucose-(1 → 4)-β-d-galacto side	C39H64O15	Fruits	[61]
130	26-O-β-d-glucopyranosyl-3β,20α,26-triol-25(R)-Δ5,22-diene-furosta-3-O-α-l-rhamnopyranosyl(1 → 2)-[α-l-rhamnopyranosyl (1 → 4)]-β-d-glucopyranosyl	C51H82O22	Fruits	[61]
131	2α,3β-dihydroxy-5α-pregn-16-en-20-one-3-O-β-D-glucopyranos yl-(1 → 4)-β-d-galactopyranoside	C33H52O13	Fruits	[61]
132	Physanol A	C36H50O4	Fruits, Seeds	[7,8,10,14,62]
133	Physanol B	C36H52O4	Fruits, Seeds	[7,8,10,14,62]
134	Physalindicanol B	C28H46O2	Calyxes, Fruits	[54]
135	Gramisterol	C29H48O	Calyxes, Fruits	[7,10,14,54]
136	Obtusifoliol	C30H50O	Calyxes, Fruits	[7,10,14]
137	Saringosterol	C29H48O2	Calyxes	[8]
138	β-Sitosterol	C29H50O	Fruits, Calyxes	[30]
139	7-Oxo-β-sitosterol	C29H48O2	Whole plants	[46]
140	7β-Hydroxysitosterol	C29H50O2	Whole plants	[46]
141	Sargassuol A	C27H43O3	Whole plants	[46]
142	Stigmasterol	C29H48O	Calyxes	[32]
143	14α-Methyl-5α-β(11) cholesterol	C28H48O	Calyxes	[7,8]
144	Cholesterol	C27H46O	Calyxes	[7,10]
145	24-Methyl-cholesterol	C28H48O	Calyxes	[7]
146	24-Ethyl-cholesterol	C29H50O	Calyxes	[10]
147	Cycloartanol	C30H52O	Seeds	[7,10]
148	Cycloartenol	C30H50O	Seeds	[7,10]
149	Lanost-8-en-3β-ol	C30H52O	Seeds	[10]
150	Daucosterol	C35H60O6	Calyxes	[58,63]
151	Isofucosterol	C29H48O	Roots, Stems	[7,58]
152	3β,24ξ-Dihydroxy-ergosta-5, 25-dienolide	C28H46O2	Whole plants	[38]
153	Ergosta-5,25-diene-3β, 24ξ-diol	C28H46O2	Calyxes, Fruits	[54]
154	(22E)-5α,8α-Epidioxyergosta-6,22-dien-3β-ol	C28H44O3	Calyxes, Fruits	[54]
155	(3β)-3-Hydroxy-26,27-dinorcholest-5-en-24-one	C25H40O2	Calyxes, Fruits	[54]
156	26,27-Dinorcholest-4-ene-3,24-dione	C25H38O2	Calyxes, Fruits	[54]
157	(3β, 22E)-3-Hydroxy-26,27-dinorcholesta-5,22-dien-24-one	C25H38O2	Calyxes, Fruits	[54]
158	3β-Hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one	C28H42O2	Calyxes, Fruits	[54]
159	3β-Hydroxystigmasta-5,22-dien-7-one	C29H46O2	Whole plants	[46]
160	Stigmasta-5,22-dien-3β,7β-diol	C29H48O2	Whole plants	[46]
161	3β-hydroxy-cholest-5-en-7-one	C27H44O2	Whole plants	[46]
162	(24R)-5,28-stigmastadiene-3β,24-diol-7-one	C29H47O10	Whole plants	[46]
163	(24S)-5,28-stigmastadiene-3β,24-diol-7-one	C29H47O10	Whole plants	[46]
164	Gitogenin	C27H44O4	Calyxes, Fruits	[54]
	Flavonoids
165	Physaflavonol	C17H14O8	Calyxes, Aerial parts	[52]
166	Ombuine	C17H14O7	Calyxes	[7,8,14,20]
167	Luteolin	C15H10O6	Calyxes	[26,63]
168	Cynaroside	C21H20O11	Calyxes	[26]
169	Catechin	C15H14O	Calyxes	[26]
170	L-Epicatechin	C15H14O6	Calyxes	[26]
171	Rutin	C27H30O16	Calyxes	[26]
172	Quercetin	C15H10O7	Fruits, Calyxes	[26,40,63]
173	Kaempferide	C16H12O6	Fruits, Calyxes	[40]
174	Kaempferol	C15H10O6	Calyxes	[7,30]
175	Myricetin	C15H10O8	Calyxes	[7,30]
176	Diosmetin	C16H12O6	Calyxes	[26]
177	Apigenin	C15H10O5	Calyxes	[7,26]
178	Chrysoeriol	C16H12O6	Calyxes, Fruits	[7,8,54]
179	Eriodictyol	C15H10O5	Calyxes, Fruits	[54]
180	Phytolaccin	C17H14O7	Roots, Stems	[42]
181	Rhamnazin	C17H14O7	Calyxes, Fruits	[54]
182	Wogonin	C16H12O5	Fruits, Calyxes	[56]
183	Nobiletin	C21H22O8	Fruits, Calyxes	[56]
184	Liquiritigenin	C15H12O4	Fruits, Calyxes	[56]
185	Luteolin-4′-O-glucoside	C21H20O11	Calyxes, Fruits	[64]
186	Luteolin-7-O-glucoside	C21H20O11	Calyxes, Fruits	[64]
187	Luteolin-7-β-D-glucoside	C21H20O11	Calyxes	[10]
188	Luteolin-4-O-β-D-glucoside	C21H20O11	Calyxes, Fruits	[40]
189	Luteolin-7-O-α-D-glucoside	C21H20O11	Calyxes	[36]
190	Luteolin-7-O-β-D-glucoside	C21H20O11	Roots, Stems	[7,58,65,66]
191	Luteolin-7-O-α-d-glucopyranoside	C21H20O11	Calyxes	[14]
192	Luteolin-7-O-β-d-glucopyranoside	C21H20O11	Calyxes	[30]
193	Luteolin-4′-O-β-d-glucopyranoside	C21H20O11	Calyxes	[30,66]
194	Luteolin-7,4′-di-O-β-d-glucopyranoside	C27H30O16	Calyxes	[7,8,14,20]
195	Luteolin-7,3′-di-O-β-d-glucopyranoside	C27H30O16	Calyxes	[66]
196	Quercetin-3-O-β-d-glucopyranoside	C21H20O12	Calyxes	[66]
197	Quercetin-3,7-di-O-β-d-glucopyranoside	C27H30O17	Calyxes	[66]
198	3′,4′-O-demethyl quercetin	C17H14O7	Calyxes	[37]
199	3′,4′-Dimethoxymyricetin	C17H14O8	Calyxes	[8,67]
200	5,7-Dimethoxycoumarin	C11H10O4	Calyxes	[26]
201	5,4′,5′-Trihydroxy-7,3′-dimethoxyflavonol	C17H14O8	Fruits, Calyxes	[7,8]
202	5,6,7-Trimethoxy-flavone	C18H16O5	Calyxes	[7]
203	Isoquercitrin	C21H20O12	Fruits, Calyxes	[7,26,30,40]
204	Kaemperide-3-O-glucoside	C22H22O11	Fruits, Calyxes	[40]
205	4′-Methoxy kaempferol	C16H12O6	Calyxes	[36]
206	Kaempferol-4′-methoxy-7-O-β-d-glucopyranoside	C22H20O11	Calyxes	[7,30]
207	Kaempferol-4′-methoxy-3-O-β-d-glucopyranoside	C22H20O11	Calyxes	[7,30]
208	Kaempferol-3-O-β-d-Glucose	C21H10O11	Calyxes	[37]
209	Dihydrokaempferol-7-O-glucoside	C21H22O11	Calyxes, Fruits	[40]
210	3,7-di-O-α-L-rhamnopyransoyl kaempferol	C27H22O14?	Calyxes	[37]
211	Apigenin-7-glucoside	C21H20O10	Calyxes	[26]
212	Apigenin-7-O-β-D-glucoside	C21H20O10	Calyxes	[68]
213	Apigenin-7-O-β-d-glucopyranoside	C21H20O10	Calyxes	[14]
214	Chrysoeriol-7-O-β-glucopyranoside	C22H22O11	Calyxes, Fruits	[41]
215	Chrysoeriol-7-O-β-D-glucoside	C22H22O11	Calyxes	[68]
216	Diosmetin-O-β-d-glucopyranoside	C22H22O11	Calyxes	[16]
217	Diosmetin-7-O-β-D-glucoside	C22H22O11	Calyxes	[68]
218	Malvidin-3-O-glucoside	C23H24O12	Calyxes, Fruits	[40]
219	Rhamnazin-3-O-glucopyranoside	C23H26O12	Calyxes, Fruits	[64]
Alkaloids
220	3α-Tigloyloxytropane	C13H21NO2	Roots	[7,8,10,14]
221	Tigloidine	C13H21NO2	Roots	[8,14]
222	Tropine	C8H15NO	Roots	[7,8,10,14]
223	Hygrine	C8H15NO	Roots	[7,8]
224	Cuscohygrine	C13H24N2O	Roots	[7,8,14]
225	Pseudotropine	C8H15NO	Roots	[7,8,10]
226	3α-Tigloyloxy tropane N-oxide	C13H21NO3	Roots	[7,8,10]
227	Phygrine	C6H28N2O2	Roots	[8,14,69]
228	Calystegin A3	C7H13NO3	Roots	[8,70]
229	Calystegin A5	C7H13NO3	Roots	[8,70]
230	Calystegin B1	C7H13NO4	Roots	[8,70]
231	Calystegin B2	C7H13NO4	Roots	[8,70]
232	Calystegin B3	C7H13NO4	Roots	[8,70]
233	Calystegin C1	C7H13NO5	Roots	[8,70]
234	1β-Amino-2α,3β,5β-trihydroxycycloheptane	C7H16NO3	Roots	[8,14,70]
235	Anaferine	C13H24N2O	Roots	[8]
236	Anahygrine	C13H24N2O	Roots	[8]
237	Trans-N-feruloyl-3-O-methyldopamine	C19H21NO5	Calyxes, Fruits	[41]
238	5-Hydroxy-2-pyridinemethanol	C6H7NO2	Calyxes, Fruits	[41]
239	Feruloyltyramine	C18H19NO4	Calyxes, Fruits	[64]
240	N-trans-feruloyltyramine	C18H19NO4	Calyxes	[31]
241	N-p-coumaroyltyramine	C17H17NO3	Calyxes	[31]
242	Neoechinulin A	C19H21N3O2	Calyxes, Fruits	[64]
243	3-(4-hydroxy-3-methoxyphenyl)-N-(4-methylphenyl)-2-propenamide	C17H17NO3	Calyxes, Fruits	[64]
244	Aurantiamide	C25H26N2O3	Calyxes, Fruits	[54]
245	Isoechinulin A	C24H29N3O3	Calyxes, Fruits	[54]
246	N-benzoyl-L-phenylalaninol	C16H17NO2	Calyxes, Fruits	[54]
247	Aurantiamide acetate	C27H28N2O4	Calyxes, Fruits	[54]
248	Ginsenine	C13H14N2O2	Fruits	[61]
Phenylpropanoids
249	Ferulic acid	C10H10O4	Calyxes	[16,26]
250	Trans-ferulic acid	C10H10O4	Whole plants	[39]
251	Chlorogenic acid	C16H18O9	Fruits, Calyxes	[16,31,41]
252	Syringalide B	C24H28O10	Fruits, Calyxes	[16,41,68]
253	Syringaresinol	C22H26O8	Fruits, Calyxes	[41]
254	3-Caffeoylquinic acid methyl ester	C18H22O9	Fruits, Calyxes	[16,31,41]
255	(+)-Medioresinol-O-β-D-di-glucopyranoside	C33H44O17	Fruits, Calyxes	[16,68]
256	(+) -Syringaresinol-O-β-D-di-glucopyranoside	C34H46O18	Fruits, Calyxes	[16,41,68]
257	(+)-Pinoresinol-O-β-D-di-glucopyranoside	C32H42O16	Fruits, Calyxes	[16,41,68]
258	Scopoletin-7-O-β-D-di-glucopyranoside	C22H28O14	Fruits, Calyxes	[68]
259	Syringaresinol-4′-O-β-d-glucopyranoside	C28H36O13	Calyxes	[31]
260	p-Coumaric acid	C9H8O3	Calyxes	[26,36,41]
261	6,6′,7,7′-Tetrahydroxy-5,5′-dicoumarol	C18H10O8	Calyxes	[36]
262	Caffeic acid	C9H8O4	Fruits, Calyxes	[30,40,41]
263	Esculetin	C9H6O4	Calyxes	[26,30]
264	8-Hydroxy-7-methoxycoumarin	C10H8O4	Fruits, Calyxes	[41]
265	3,4-Dimethoxy-5-hydroxy-cinnamyi alcohol-9-O-β-d-glucopyranoside	C17H24O9	Fruits, Calyxes	[41]
266	Sachaliside 1	C15H20O7	Fruits, Calyxes	[41]
267	3-caffeoyl quinic acid	C16H18O9	Fruits, Calyxes	[40]
268	4,5,3′,4′-Tetrahydroxy-2,7′-cycloligna-7,7′-dien-9,9′-olide	C18H12O6	Calyxes	[30]
269	Syringaresinol-4,4′-O-di-β-D-glucoside	C34H46O18	Calyxes	[30]
270	Cinnamic acid	C9H8O2	Fruits	[71]
271	p-Hydroxy-cinnamic acid	C9H8O3	Fruits	[71]
272	Schizandrin	C24H32O7	Fruits, Calyxes	[56]
Terpenoids
273	Physalisitin A	C15H24O3	Calyxes	[16]
274	Physalisitin B	C15H24O2	Calyxes	[16]
275	Physalisitin C	C15H22O2	Calyxes	[16]
276	Citroside A	C19H30O8	Fruits, Calyxes	[16,41]
277	(6S,9R)-Roseoside	C19H30O8	Fruits, Calyxes	[16,41]
278	(6S,9S)-Roseoside	C19H30O8	Fruits, Calyxes	[16,41]
279	(6R,9S)-3-Oxo-α-ionol-β-d-glucopyranoside	C19H30O7	Fruits, Calyxes	[16,41]
280	Oleanolic acid	C30H48O3	Calyxes	[37,58]
281	Physanoside A	C25H40O12	Leaves, Stems	[16,72]
282	Physanoside B	C25H40O12	Leaves, Stems	[16,72]
283	Neryl-1-O-β-d-glucopyranosyl-(1 → 2)-O-［α-L-arabinopy-ranosyl-(1 → 6)］-O-β-d-glucopyranoside	C27H46O15	Calyxes	[16,31]
284	Ursolic acid	C30H48O	Calyxes	[16]
285	Blumenol A	C13H20O3	Fruits, Calyxes	[56,64]
286	Dehydrovomifoliol	C13H18O3	Fruits, Calyxes, Roots, Stems	[41,42]
287	3β-Hydroxy-5,6-epoxy-7-megastigmen-9-one	C13H20O3	Fruits, Calyxes	[41]
288	Rel-(3E)-4-[(1R,2R,4S)-1,2,4-trihydroxy-2,6,6-trimethylcyclohexyl]-3-buten-2-one	C13H22O4	Fruits, Calyxes	[41]
289	4aβ-Decahydro-8aα-methyl-4-methylene-6β-(1-methylethenyl)-1α,3α-naphthalenediol	C15H24O2	Calyxes, Fruits	[54]
290	Capsidiol	C15H24O2	Calyxes, Fruits	[54]
291	(+)-Anhydro-β-rotunol	C15H20O2	Calyxes, Fruits	[54]
292	Pubinernoid A	C11H16O3	Fruits, Calyxes	[41,54]
293	4-(3,4-dihydroxy-4-methylpentyl)-3-(hydroxymethyl)-2,4-dimethylcyclohexa-2,5-dien-1-one	C15H24O4	Roots, Stems	[42]
294	7-(3-hydroxyprop-1-en-2-yl)-1,4a-dimethyl-5,6,7,8-tetrahydronaphthalen-2(4aH)-one	C15H20O2	Roots, Stems	[42]
295	3-O-α-l-Arabinopyranose-Hedera sapogenin-28-O-(4-O-acetyl)-α-l-rhamnopyranose-(1 → 4)-β-d-glucopyranose-(1 → 6)-β-d-glucopyranosyl	C49H78O19	Fruits	[61]
Physakengoses
296	Physakengose A	C29H50O13	Aerial parts	[18]
297	Physakengose B	C33H56O14	Aerial parts	[18]
298	Physakengose C	C31H52O14	Aerial parts	[18]
299	Physakengose D	C29H50O13	Aerial parts	[18]
300	Physakengose E	C34H58O14	Aerial parts	[18]
301	Physakengose F	C34H56O14	Aerial parts	[18]
302	Physakengose G	C36H60O15	Aerial parts	[18]
303	Physakengose H	C36H58O15	Aerial parts	[18]
304	Physakengose I	C36H62O14	Aerial parts	[18]
305	Physakengose J	C36H60O14	Aerial parts	[18]
306	Physakengose K	C38H64O15	Aerial parts	[17]
307	Physakengose L	C35H58O15	Aerial parts	[17]
308	Physakengose M	C35H58O15	Aerial parts	[17]
309	Physakengose N	C35H58O14	Aerial parts	[17]
310	Physakengose O	C34H58O14	Aerial parts	[17]
311	Physakengose P	C22H34O13	Aerial parts	[17]
312	Physakengose Q	C22H36O13	Aerial parts	[17]
Piperazines
313	(3S,6R)-3-isopropyl-6-(2-methyl propyl)-2,5-piperazine diketone	C11H20N2O2	Calyxes	[19]
314	(3S, 6S)-3-isobutyl-6-isopropyl-2,5-piperazine diketone	C11H20N2O2	Calyxes	[19]
315	(3S,6S)-3,6-di-(2-methyl propyl)-2,5-piperazine diketone	C12H22N2O2	Calyxes	[19]
316	(3S,6S)-3,6-di-isopropyl-2,5-piperazine diketone	C10H18N2O2	Calyxes	[19]
317	(3S,6R)-3-(2-methyl propyl)- 6-benzyl-2,5-piperazine diketone	C15H20N2O2	Calyxes	[19]
318	(3S,6S)-3-isobutyl-6-benzyl-2,5-piperazine diketone	C15H20N2O2	Calyxes	[19]
319	(3S,6S)-3-isopropyl-6-(p-hydroxy benzyl)-2,5-piperazine diketone	C14H18N2O3	Calyxes	[19]
320	(3S,6R)-3-isopropyl-6-(p-hydroxy benzyl)-2,5-piperazine diketone	C14H18N2O3	Calyxes	[19]
321	(3S,6R)-3-(2-methyl propyl)-6-(p-hydroxy benzyl)-2,5-piperazine diketone	C15H20N2O3	Calyxes	[19]
322	(3S,6S)-3-isobutyl-6-(p-hydroxy benzyl)-2,5-piperazine diketone	C15H20N2O3	Calyxes	[19]
323	(3S,6S)-3-isopropyl-6-benzyl-2,5-piperazine diketone	C14H18N2O2	Calyxes	[19]
324	(3S,6R)-3-isobutyl-6-(2-methyl propyl)-2,5-piperazine diketone	C12H22N2O2	Calyxes	[19]
325	(3S,6S)-3-benzyl-6-(p-hydroxy benzyl)-2, 5-piperazine diketone	C18H18N2O3	Calyxes	[19]
Volatile oils
326	3,4-Dihydroxyphenethyl alcohol	C8H10O3	Calyxes	[37]
327	Octanoic acid	C8H16O2	Calyxes with fruit stalk	[20,21]
328	3,7-dimethyl- (E)-2,6-Octadien-1-ol	C10H18O	Calyxes	[20]
329	2,4-decadienal	C10H16O	Calyxes	[20]
330	6,10-dimethyl-(Z)-5,9-undecadien-2-one	C13H22O	Calyxes	[20]
331	4-(2,6,6-trimehyl-cyclohexen-1-yl)-(E)-3-buten-2-one	C13H20O	Calyxes	[20]
332	6,11-dimethyl-2,6,10-dodecatrien-1-ol	C14H24O	Calyxes	[20]
333	Tetradecanoic acid	C14H28O2	Calyxes	[20]
334	2,3,5,8-tetramethyl-decane	C14H30	Calyxes	[20]
335	6,10,14-trimethyl-2-pentadecanone	C18H36O	Calyxes	[20]
336	6,10,14- trimethyl-5,9,13-petadecatrien-2-one	C18H30O	Calyxes	[20]
337	1-chloro-octadecane	C18H37Cl	Calyxes	[20]
338	14-methyl-pentadecanoic acid-methyl ester	C17H34O2	Calyxes	[20]
339	1,(E)-11,(Z)-13-octadecatriene	C18H32	Calyxes	[20]
340	(Z)-9-octadecenal	C18H34O	Calyxes	[20]
341	n Decanoic acid	C10H20O2	Calyxes with fruit stalk	[21]
342	(E)-6,10-Dimethyl-5,9-undecadien-2-one	C13H22O	Calyxes with fruit stalk	[21]
343	(E)-4-(2,6,6-Trimethyl-1-cyclohexane-1alkenyl)-3-butene-2-one	C13H20O	Calyxes with fruit stalk	[21]
344	3,3,7,7-Tetramethyl-5-(2-methyl-1-allyl)-tricyclic[4.1.0.0.2.4]-heptane	C15H24	Calyxes with fruit stalk	[21]
345	3,7,11- Trimethyl-1,6,10-dodecatrien-3-ol	C15H26O	Calyxes with fruit stalk	[21]
346	α-Bisabolol	C15H26O	Calyxes with fruit stalk	[21]
347	(−)-Spatula eucalyptol	C15H24O	Calyxes with fruit stalk	[21]
348	Isoaromadendrene oxide	C15H24O	Calyxes with fruit stalk	[21]
349	Decalin-1,1,4,7-tetramethyl-1H-cyclopropyl[e] azulene-4-ol	C15H26O	Calyxes with fruit stalk	[21]
350	Cubenol	C15H26O	Calyxes with fruit stalk	[21]
351	Cadinol	C15H26O	Calyxes with fruit stalk	[21]
352	Epiglobulol	C15H26O	Calyxes with fruit stalk	[21]
353	Oleyl alcohol	C18H34O2	Calyxes with fruit stalk	[21]
354	2-Nonadecanone	C19H38O	Calyxes with fruit stalk	[21]
355	1,5-Dimethyl-3-hydroxy-8-(1-methylene-2-hydroxyethyl)-di-cyclo[4.4.0]decane-5-ene	C15H24O2	Calyxes with fruit stalk	[21]
356	Trans-Longipino carvenol	C15H24O	Calyxes with fruit stalk	[21]
357	Myristic acid	C14H28O2	Calyxes with fruit stalk	[21]
358	Solavetivone	C15H22O	Calyxes with fruit stalk	[21]
359	Pentadecanoic acid	C15H30O2	Calyxes with fruit stalk	[21]
360	Hexahydrofarnesylacetone	C18H36O	Calyxes with fruit stalk	[21]
361	Farnesylacetone	C18H30O	Calyxes with fruit stalk	[21]
362	(Z)-7-Methyl hexadecenoate	C17H32O2	Calyxes with fruit stalk	[21]
363	Butyl octyl phthalate	C20H30O4	Calyxes with fruit stalk	[21]
364	n-Palmitic Acid	C16H32O2	Calyxes, Fruits	[21,23,54]
365	9,12-Octadecadienoic acid methyl ester	C19H34O2	Calyxes with fruit stalk	[21]
366	5- Dodecyl-2(3H)-furan	C16H30O2	Calyxes with fruit stalk	[21]
367	9,12-Linoleic acid	C18H32O2	Calyxes with fruit stalk	[21]
368	Heptacosane	C27H56	Calyxes with fruit stalk	[21]
369	Octacosane	C28H68	Calyxes with fruit stalk	[21]
370	Methyl palmitate	C17H34O2	Roots, Stems	[23]
371	Ethyl palmitate	C16H32O2	Roots, Stems	[23]
372	(Z)9-Octadecenamide	C13H35NO	Roots, Stems	[23]
373	6,9-Methyl octadecadienoate	C19H34O2	Roots, Stems	[23]
374	8,9-Didehydro-9-formylisolongifolene	C15H18O2	Roots, Stems	[23]
375	Solavetivone	C15H22O	Roots, Stems	[23]
376	(E)11-Hexadecenoic acid	C16H30O2	Roots, Stems	[23]
377	5-Dodecyl-2-furanone	C16H30O2	Roots, Stems	[23]
378	Aromadendrene-2-oxide	C15H24O	Roots, Stems	[23]
379	1-Cyclohexyl heptene	C13H24	Roots, Stems	[23]
380	(E)4-(2,6,6-trimethyl-2-cyclohexenyl)-3-butene-2ketone	C13H20O	Roots, Stems	[23]
381	1-Pentadecene	C15H30	Roots, Stems	[23]
382	Pentadecane	C15H32	Roots, Stems	[23]
383	Hexadecane	C16H34	Roots, Stems	[23]
384	Heptadecane	C17H36	Roots, Stems	[23]
385	Octadecane	C18H38	Roots, Stems	[23]
386	Nonadecane	C19H40	Roots, Stems	[23]
387	Pentacosane	C25H52	Roots, Stems	[23]
388	Tetratetracontane	C44H90	Roots, Stems	[23]
389	(E)2,4-Diphenyl-4-methyl amylene	C18H20	Roots, Stems	[23]
390	(Z,Z,Z)9,12,15-Octadecatrienoicacid, methyl ester	C19H32O2	Roots, Stems	[23]
391	α-Pinene	C10H16	Fruits	[28]
392	Camphene	C10H16	Fruits	[28]
393	Sabinene	C10H16	Fruits	[28]
394	β-Pinene	C10H16	Fruits	[28]
395	Myrcene	C10H16	Fruits	[28]
396	p-Cymene	C10H14	Fruits	[28]
397	Limonene	C10H16	Fruits	[28]
398	γ-Terpinene	C10H16	Fruits	[28]
399	Camphenilone	C9H14O	Fruits	[28]
400	β-Linalool	C10H18O	Fruits	[28]
401	Nonanal	C9H18O	Fruits	[28]
402	Camphor	C10H16O	Fruits	[28]
403	1-Terpinen-4-ol	C10H18O	Fruits	[28]
404	α-Terpineol	C10H18O	Fruits	[28]
405	Nerol	C10H18O	Fruits	[28]
406	n-Tridecane	C13H28	Fruits	[28]
407	Isoamyl benzyl ether	C12H18O	Fruits	[28]
408	Neryl acetate	C12H20O2	Fruits	[28]
409	Sibirene	C15H24	Fruits	[28]
410	β-Caryophyllene	C15H24	Fruits	[28]
411	Germacrene D	C15H24	Fruits	[28]
412	β-Selinene	C15H24	Fruits	[28]
413	α-Zingiberene	C15H24	Fruits	[28]
414	Bicyclogermacrene	C15H24	Fruits	[28]
415	δ-Cadinene	C15H24	Fruits	[28]
416	α-Cadinene	C15H24	Fruits	[28]
417	1-epi-Cubenol	C15H26O	Fruits	[28]
418	(2E,6E)-Methyl farnesoate	C16H26O2	Fruits	[28]
419	(2Z,6E)-Farnesyl acetate	C17H28O2	Fruits	[28]
420	(5Z,9E)-Farnesyl acetone	C18H30O	Fruits	[28]
421	Phytol	C20H40O	Fruits	[28]
Polysaccharides
422	Mannose	C6H12O6	Roots, Stems	[23]
423	GlcUA	C6H10O7	Roots, Stems	[23]
424	Galactose	C6H12O6	Roots, Stems	[23]
425	Xylose	C5H10O5	Roots, Stems	[23]
426	Arabinose	C5H10O5	Roots, Stems	[23]
427	Rhamnose	C6H12O5	Roots, Stems	[23]
428	α-d-glucose	C6H12O6	Calyxes	[65]
429	GalA	C6H10O7	Fruits	[73]
430	Fucose	C6H12O5	Roots	[22]
431	Sucrose	C12H22O11	Fruits	[61]
432	Maltose	C12H22O11	Fruits	[61]
Amino acids
433	Arginine	C6H14N4O2	Calyxes	[26]
434	l-Phenylalanine	C9H11NO2	Calyxes	[26]
435	Glutamic acid	C5H9NO4	Calyxes	[26]
436	Valine	C5H11NO2	Calyxes	[26]
437	l-Proline	C5H9NO2	Calyxes	[71]
438	M-Phenylalanine	C9H11NO2	Calyxes	[71]
439	l-Leucine	C6H13NO2	Fruits	[71]
440	L-Tryptophan	C11H19N2O2	Fruits	[71]
441	Aspartic acid	C4H7NO4	Seeds	[28]
442	Serine	C3H7NO3	Seeds	[28]
443	Glycine	C2H5NO2	Seeds	[28]
444	Histidine	C6H9N3O2	Seeds	[28]
445	Threonine	C4H9NO3	Seeds	[28]
446	Alanine	C3H7NO2	Seeds	[28]
447	Cysteine	C3H7NO2S	Seeds	[28]
448	Tyrosine	C9H11NO3	Seeds	[28]
449	Methionine	C5H11NO2S	Seeds	[28]
450	Lysine	C6H14N2O2	Seeds	[28]
451	Isoleucine	C6H13NO2	Seeds	[28]
Fatty Acids
452	Capric	C20H40O2	Seeds, Peels	[28]
453	Undecylic	C11H22O2	Seeds, Peels	[28]
454	Lauric	C12H24O2	Seeds, Peels	[28]
455	Tridecylic	C13H26O2	Seeds, Peels	[28]
456	Myristoleic	C14H26O2	Seeds, Peels	[28]
457	Palmitoleic	C16H30O2	Seeds, Peels	[28]
458	Margaric	C17H34O2	Seeds, Peels	[28]
459	Heptadecenoic	C17H32O2	Seeds, Peels	[28]
460	Stearic	C18H36O2	Seeds, Peels	[28]
461	Oleic	C18H34O2	Seeds, Peels	[28]
462	Linoleic	C18H32O2	Seeds, Peels	[28]
463	Linolenic	C18H30O2	Seeds, Peels	[28]
464	Eicosadienoic	C20H36O2	Seeds, Peels	[28]
465	Eicosatrienoic	C20H34O2	Seeds, Peels	[28]
466	Eicosatetraenoic	C20H32O2	Seeds, Peels	[28]
467	Eicosapentaenoic	C20H30O2	Seeds, Peels	[28]
468	n-Hexacosanoic acid	C26H52O2	Fruits, Calyxes	[41]
469	Hendecanoic acid	C11H22O2	Calyxes, Fruits	[54]
470	Tetra-cosanic acid	C24H48O2	Calyxes	[37]
471	(Z)-9,10,11-trihydroxy-12-octadecenoic acid	C18H34O5	Calyxes	[37,58]
472	Tricosanoic Acid	C23H46O2	Aerial parts	[52]
473	Glyceryl monostearate	C21H42O4	Roots, Stems	[58]
474	Glyceryl ester of Behenic Acid	C25H50O4	Calyxes	[52]
475	Succinct acid	C4H6O4	Fruits	[29]
476	(8,11)-Dienoic acid	C16H28O2	Fruits	[29]
Organic acids
477	Nicotinic acid	C6H5NO2	Fruits	[71]
478	Vanillic acid	C8H8O4	Fruits, Calyxes	[41]
479	Citric acid	C6H8O7	Calyxes	[26,30,40]
480	Succinic acid	C4H6O4	Fruits, Calyxes	[40]
481	Cumaric acid	C9H8O3	Fruits, Calyxes	[40]
482	Quinic acid	C7H12O6	Calyxes	[26]
483	Gallic acid	C7H6O5	Calyxes	[26]
484	Gentisic Acid	C7H6O4	Calyxes	[26]
485	3-Indoleacrylic acid	C11H9NO2	Calyxes	[26]
486	5-Methyl-3-pyridinecarboxylicacid	C7H7NO2	Fruits	[34]
487	5-Hydroxymethylfuroic acid	C6H6O4	Fruits	[34,64,74]
488	2-((2-Ethylhexyloxy)carbonyl)benzoic acid	C16H22O4	Fruits	[29]
Aliphatics
489	N-tetracosane	C24H50	Calyxes, Fruits	[64]
490	Dibutyl phthalate	C16H22O4	Calyxes, Fruits	[64]
491	Bis(2-ethylhexyl)phthalate	C6H6O4	Calyxes, Fruits	[64]
492	1-O-(9Z,12Z-octadecadienoyl)glycerol	C21H38O4	Calyxes, Fruits	[54]
493	Methyl(10E,12Z)-9-hydroxy-octadecadienoate	C19H34O3	Calyxes, Fruits	[54]
494	1,5-Dimethyl citrate	C8H12O7	Fruits	[34,74]
495	5-Hydroxymethylfurfural	C6H6O3	Fruits, Calyxes	[56]
496	5-(hydroxymethyl)-2-(dimethoxymethyl)furan	C8H12O4	Fruits, Calyxes	[56]
497	1-Citric acid ethyl ester	C8H12O7	Fruits	[29]
498	1-Citric acid methyl ester	C7H10O7	Fruits	[29]
499	9,12-Ethyl octadeca-9,12-dienoate	C20H36O2	Fruits	[29]
Nucleosides
500	Adenine	C5H5N5	Calyxes	[31]
501	Adenosine	C10H13N5O4	Calyxes	[31]
502	Guanosine	C10H13N5O5	Calyxes	[26]
503	Uridine	C9H12N2O6	Calyxes	[26]
Anthraquinones
504	Emodin	C15H10O5	Calyxes	[26]
505	Aurantio-obtusin-6-O-β-D-glucoside	C23H24O12	Calyxes	[26]
Phenols
506	Ethyl caffeate	C11H12O4	Calyxes	[30]
507	Ethyl ferulate	C12H14O4	Calyxes	[30]
508	Syringic acid	C9H10O5	Calyxes, Fruits	[30,71]
509	Hydroxytyrosol	C8H10O3	Fruits	[71]
510	Hydroquinone	C6H6O2	Calyxes	[52]
Tocopherols
511	α-Tocopherol	C29H50O2	Seeds, Peels	[28]
512	β-Tocopherol	C28H48O2	Seeds, Peels	[28]
513	γ-Tocopherol	C28H48O2	Seeds, Peels	[28]
Trace elements
514	Potassium (K)	K	Seeds	[28]
515	Sodium (Na)	Na	Seeds	[28]
516	Calcium (Ca)	Ca	Seeds	[28]
517	Magnesium (Mg)	Mg	Seeds	[28]
518	Iron (Fe)	Fe	Seeds	[28]
519	Manganese (Mn)	Mn	Seeds	[28]
520	Copper (Cu)	Cu	Seeds	[28]
521	Zinc (Zn)	Zn	Seeds	[28]
522	Lead (Pb)	Pb	Seeds	[28]
523	Cadmium (Cd)	Cd	Seeds	[28]
524	Chromium (Cr)	Cr	Seeds	[28]
Others
525	7-Epiloliolide	C11H16O3	Fruits, Calyxes	[41]
526	Tetillapyrone	C11H14O6	Fruits, Calyxes	[41]
527	3,5-dimethoxy-4-hydroxybenzaldehyde	C9H10O4	Roots, Stems	[42]
528	1-O-β-D-glucopyra-n-osyl-2-N-(2′-hydroxypalmitoyl)octadeca sphi-nga-4,8-dienine	C40H75NO9	Fruits	[29]
529	Dihydrofuran-2,5-dione	C4H4O3	Fruits	[29]
530	Cyclo-(L-leucyl-L-isoleucyl)	C12H22N2O2	Fruits	[29]
531	Cyclo(tyrosine-amidocaproic) -bipeptid	C15H20N2O3	Calyxes	[74]
532	Cuneataside E	C24H40O11	Calyxes	[52]
533	1-O-[3-O-2-methyl-5-(2,3,4-trimethyl)phenyl-2,3-pentanediol]-β-d-xylopyranosyl-(1 → 6)-β-d-galactopyranoside	C26H42O11	Fruits, Calyxes	[56]
534	(Z)-Hex-3-en-1-ol O-β-d-xylcopyranosyl-(1–6)-β-D-glucopyran-osyl-(1–2)-β-d-glucopyranoside	C23H40O15	Calyxes	[75]
535	(E)-Hex-3-en-1-ol O-β-d-xylcopyranosyl-(1–6)-β-D-glucopyran-osyl-(1–2)-β-d-glucopyranoside	C23H40O15	Calyxes	[75]

3.1. Steroids

Steroids are the main components of P. alkekengi. A total of 164 steroids have been isolated and identified from the calyx, fruit, and above-ground parts of P. alkekengi, accounting for 30.65% of the total compound types. These include physalins, neophysalins, sterols, and withanolides, among which physalins are the most abundant. The study of physalins in P. alkekengi began in 1969 with the isolation and identification of physalin A by Japanese scholars, and since then several physalins compounds have been identified. Phylasins are a class of steroidal compounds with a bitter taste [8]. The basic structure of physalins consists of a 13,14-seco-16,24-cycloergostane skeleton. Neophysalins were first discovered by Japanese scholars in 1991 [13]. The difference between neophysalins and physalins is that the C-15 of physalins is directly linked to C-16, and C-14 forms a lactone ring with C-17, whereas the C-14 of neophysalins is directly linked to C-16, and C-15 forms a lactone ring with C-17 [8].

Sterols are mainly found in the fruit, seeds, and calyx of P. alkekengi [14]. At present, physanol A and physanol B have been isolated from the fruits of P. alkekengi, and a variety of 4α-methyl sterols, mainly gramisterol and obtusifoliol, have been isolated from the unsaponifiables of the seed oil, in addition to a variety of 4-desmethyl sterols [10]. Withanolides are a class of ergostane lactones containing 28 carbon atoms derived from the ergostane backbone and characterised by the formation of δ- or γ-lactones by linking the C-22 to the C-26, or the C-23 to the C-26 in the side chain [15]. Specific information on the steroids in P. alkekengi is given in Table 1.

3.2. Flavonoids

Flavonoids are a class of compounds characterised by the parent nucleus of 2-phenylchromogenic ketones. Fifty-five flavonoids have been isolated from P. alkekengi, accounting for 10.28% of the total compound types, which is one of the important active ingredients in P. alkekengi. Flavonoids in P. alkekengi are mostly isolated from the fruit, calyx, and calyx-fruit combination [7], mainly including flavonoids and flavonoid glycosides. Specific information on the flavonoids in P. alkekengi is given in Table 1.

3.3. Alkaloids

Alkaloids are a class of naturally-occurring nitrogen-containing organic compounds. Twenty-nine alkaloids have been isolated from P. alkekengi, accounting for 5.42% of the total compound types. Alkaloids in P. alkekengi are predominantly concentrated in the roots and lower portions of the primary stem [7]. These mainly include tigloidine, tropine, hygrine, cuscohygrine, pseudotropine, and phygrine. Specific information on the alkaloid constituents in P. alkekengi is given in Table 1.

3.4. Phenylpropanoids

Phenylpropanoids have a benzo-alpha-pyrone structure as their parent nucleus. Twenty-four phenylpropanoids have been isolated from the calyxes of P. alkekengi, accounting for 4.49% of the total compound types. These mainly include a variety of phenylpropionic acids such as ferulic acid, chlorogenic acid, and caffeic acid [16]. Specific information on the phenylpropanoids in P. alkekengi is given in Table 1.

3.5. Physakengoses

Physakengoses are primarily composed of sucrose and long-chain fatty acid esters [16]. Zhang et al. [17,18] isolated 17 new physakengoses from P. alkekengi, including physakengoses A-Q. Specific information on the physakengoses in P. alkekengi is given in Table 1.

3.6. Piperazines

Piperazines are a class of compounds featuring the piperazine structure. Shu et al. [19] isolated thirteen piperazines from P. alkekengi, marking the first ever discovery of these compounds in Physalis L. Specific information on the piperazines in P. alkekengi is given in Table 1.

3.7. Volatile oils

Volatile oils refer to a cluster of fragrant substances that exhibit volatility. Ninety-six volatile oils have been isolated from P. alkekengi, accounting for 17.94% of the total compound types. These mainly include fatty acids and sesquiterpenoids [8], among which fatty acids such as octanoic, decanoic, pentadecanoic, n-palmitic, and myristic acids are the main components. In addition, the volatile components are mainly in the calyx, with less in the fruit [20,21]. Specific information on the volatile oils in P. alkekengi is given in Table 1.

3.8. Polysaccharides

Polysaccharides play an important role in various life processes and possess multiple health benefits. The polysaccharides are mainly extracted from the fruit and calyx parts of P. alkekengi [22], among which 8.9% polysaccharides content in the fruits [7], such as mannose, glucose, galactose, xylose, arabinose, rhamnose, fucose, sucrose, and maltose [23]. Specific information on the polysaccharide analogues in P. alkekengi is given in Table 1.

3.9. Amino acids

Amino acids are a class of organic compounds containing basic amino and acidic carboxyl groups. Physalis alkekengi contains a variety of amino acids, with nineteen amino acids having been isolated and identified, accounting for 3.55% of the total compound types. The fruits of P. alkekengi contain 18 essential amino acids, accounting for 30.66% of the total amino acids [24], among which arginine, glutamic acid, and aspartic acid are the mainly components [25]. In addition, the calyxes contain 16 amino acids, mainly including phenylalanine, glutamic acid, proline, valine, and tryptophan [26], of which the essential amino acids account for 29.13% of the total amino acids [27]. Specific information on the amino acids in P. alkekengi is given in Table 1.

3.10. Other chemical components

In addition, P. alkekengi also contains trace elements such as potassium, sodium, calcium, magnesium, iron, manganese, copper, zinc, lead, cadmium, and chromium [28]. It also contains aliphatics such as n-tetracosane, dibutyl phthalate, 1-citric acid ethyl ester, 1-citric acid methyl ester, ethyl linoleate, and 5-hydroxymethyl furfural [29], organic acids such as citric, succinic, cumaric, quinic, gallic, and gentisic acids [26], terpenoids such as citroside A, (6S,9R)-roseoside, (6S,9S)-roseoside, and ursolic acid [16], phenols such as ethyl caffeate, ethyl ferulate, and syringic acid [30], tocopherols α, β, and γ [28], anthraquinones such as emodin and aurantio-obtusin-6-o-β-d-glucoside [26], nucleosides such as adenosine, guanosine, and uridine [31], and many other compounds.

4. Pharmacological effects

Modern pharmacological studies have shown that P. alkekengi has various pharmacological effects such as anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, immunomodulatory, and anti-tumour activities. A schematic diagram of the main pharmacological mechanism of effects of P. alkekengi is shown in Fig. 3.

Fig. 3.

Main pharmacological mechanism of effects of P. alkekengi.

Abbreviations: SOD, Superoxide dismutase; CAT, Catalase; GSH-Px, Glutathione peroxidase; COX-2, Cyclooxygenase; 5-LOX, 5-Lipoxygenase; PLA2, Phospholipase A2; PGE2, Prostaglandin E2; LTB4, Leukotriene B4; IL, Interleukin; Akt, also known as PKB, Protein kinase B; MAPK, Mitogen-activated protein kinase; NF-κB, Nuclear factor kappa-B; iNOS, Inducible nitric oxide synthase; NO, Nitric oxide; TNF-α, Tumour necrosis factor-α; MDA, Malondialdehyde; DPPH, 2,2-Diphenyl-1-picrylhydrazyl; 'OH, Hydroxyl radical; ABTS, 2,2-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); O2-, Superoxide anion; NaNO2, Sodium nitrite; KEAP1, Kelch-like ECH-associated protein 1; NRF2, Nuclear factor-erythroid 2-related factor 2; GLUT4, Glucose transporter 4; PI3K, Phosphatidylinositol-3-kinase; InsR, Insulin receptor; GK, Glucokinase; GLUT2, Glucose transporter 2; PK, Pyruvate kinase; PEPCK, Phosphoenolpyruvate carboxykinase; LTA4H, Leukotriene A-4 hydrolase; IgG, Immunoglobulin G; IgG1, Immunoglobulin G1; IgG2b, Immunoglobulin G2b; STAT3, Signal transducers and activators of transcription 3; ROS, Reactive oxygen species; JAK2, Janus kinase 2; CDK1, Cycle protein-dependent kinase 1; PARP, Poly ADP-ribose polymerase; mTOR, Mammalian target of rapamycin; CDK2, Cyclin-dependent kinase 2; IFN-γ, Interferon γ; PKC, Protein kinase C.

4.1. Anti-inflammatory effects

The inflammatory response is a defensive reaction of the body to cellular damage and is the basis for the pathogenesis of multiple diseases. The crude extract of P. alkekengi by water extraction and alcohol precipitation could significantly inhibit xylene-induced acute oedema and exudative inflammation and reduce the number of inflammatory cells in rats with acute pharyngitis [76]. The aqueous extract of P. alkekengi alleviated symptoms of dextran sulphate sodium-induced ulcerative colitis in mice. It can reduce the secretion of the inflammatory factors interleukin (IL)-6 and IL-1β by increasing the antioxidant activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and significantly inhibit their mRNA expression in mouse colonic tissues, thus alleviating colitis [77]. The aqueous extract of the calyx of P. alkekengi may exert anti-inflammatory effects by inhibiting cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression and activities and inhibiting phospholipase A₂ (PLA₂), thereby doubly inhibiting the arachidonic acid metabolic pathway and reducing the production of prostaglandin E₂ (PGE₂) and leukotriene B₄ (LTB₄) [78]. The alcohol extracts of the fruits of P. alkekengi were found to inhibit the secretion of the hyperglycaemia-induced pro-inflammatory factors IL-31 and IL-33, while upregulating the anti-inflammatory factor IL-10, thereby suppressing inflammation [79]. In addition, the ethanol, petroleum ether, and ethyl acetate extracts of P. alkekengi can alleviate lipopolysaccharide (LPS)-induced inflammatory responses, mainly by blocking protein kinase B (Akt, also known as PKB) and p38 mitogen-activated protein kinase (MAPK) signalling pathways, inhibiting nuclear factor kappa-B (NF-κB) transcription and inducible nitric oxide synthase (iNOS) and COX-2 expression, and reducing the production of nitric oxide (NO), PGE₂, tumour necrosis factor-α (TNF-α), IL-1, IL-6, and reactive oxygen species [54,64,80].

The total steroidal saponins from the calyx of P. alkekengi can dose-dependently inhibit the production of the inflammatory factors NO, IL-6, IL-1β, and monocyte chemotactic protein-1 (MCP-1), thereby suppressing the expression of COX-2 to alleviate the inflammatory response, and have a significant inhibitory effect on LPS-induced inflammatory response in RAW264.7 macrophages [81]. Wang et al. [82] showed that physalin A reduced the overproduction of PGE₂, TNF-α, and NO, inhibited the expression of COX-2 and iNOS, significantly inhibited nuclear translocation of NF-κB p65 and phosphorylation of inhibitor of NF-κB (IκB-α), and exerted anti-inflammatory effects by blocking LPS-induced activation of the NF-κB signalling pathway in RAW 264.7 cells.

Yao et al. [83] found galuteolin in P. alkekengi reduced the secretion of TNF-α, IL-6, and NO as well as gene copy number of TNF-α, IL-6, and iNOS in LPS-induced RAW264.7 cells, resulting in effective anti-inflammatory effects. Chen et al. [84] found that the combination of physalin A, luteolin, and cynaroside had significant synergistic inhibitory effects on LPS-induced NO and TNF-α release from macrophages, and the combination significantly reduced LPS-induced expression of iNOS protein. In addition, Zhang et al. [85] found a dose-dependent inhibition of COX-2 enzymes by sesquiterpenoids in P. alkekengi, and Xu [15] showed that withanolides also have strong anti-inflammatory activity. In conclusion, numerous studies have shown that all extracted parts of P. alkekengi show significant anti-inflammatory activity and can be widely studied and applied as anti-inflammatory agents. Among the active components, steroids and flavonoids are most studied for their anti-inflammatory effects. The possible main components are physalins and luteolin, which mainly exert anti-inflammatory effects by inhibiting the expression of COX-2, iNOS, and NF-κB p65, reducing various pro-inflammatory factors, and thereby increasing antioxidant capacity.

4.2. Anti microbial effects

Pathogenic microorganisms can cause infections and many diseases when they invade the body. The ethanol extract of the calyx of P. alkekengi has an inhibitory effect on alpha and beta Streptococcus, Staphylococcus aureus, Bacillus subtilis, and Bacillus cereus, with the strongest inhibitory effect on beta Streptococcus and Bacillus cereus [65,86]. In addition, the ethanol extract and the polysaccharide of P. alkekengi promote the growth of probiotics such as Bacteroides, Clostridium, and Lactobacillus, inhibit the growth of pathogenic bacteria such as Escherichia coli, and improve the balance of intestinal microecology [49,87,88]. It has been determined that the methanol and dichloromethane extracts and physalin D of P. alkekengi had antibacterial effects against gram-positive bacterial species, gram-negative bacterial species, and Candida species by broth microdilution and disk diffusion methods, with the best antibacterial effect against gram-positive bacteria [89]. And the ethyl acetate-extracted parts of P. alkekengi also showed antibacterial activity against Helicobacter pylori [90].

Meng et al. [91] found that the total saponin content of P. alkekengi had an inhibitory effect on four common food spoilage bacteria, including E. coli, Salmonella typhimurine, Shigella fowlerii, and Listeria monocytogenes. Yang et al. [92] found that physalin B and physalin E have good antibacterial effects on alpha and beta-haemolytic streptococcus, S. pneumoniae, S. aureus, and Moraxella catarrhalis, and the minimum inhibitory concentration of physalin B was lower than the minimum inhibitory concentration of physalin E and has stronger bacteriostatic activity. Chlorogenic acid has also been found to have significant antimicrobial activity against S. aureus, S. pneumoniae, B. subtilis, E. coli, Shigella dysenteriae, and S. typhimurium [93]. Furthermore, physakengoses B, E-H and K-Q, new compounds discovered in P. alkekengi by Zhang et al. [17,18], have strong bacteriostatic activity against S. aureus, B. subtilis, Pseudomonas aeruginosa, and E. coli.

Meira et al. [94] showed that physalins B, D, F, and G have anti-Trypanosoma cruzi activity, of which physalins B and F are the most effective compounds for trypanosomes and epithelial cell forms. Treatment with physalins can reduce its invasion and development, which may be related to the inhibition of T. cruzi protease activity, leading to alterations in its Golgi apparatus. Guimarães et al. [95] found that physalins B and F can reduce the percentage of Leishmania infection macrophages and the number of intracellular parasites in vitro at macrophages at non-cytotoxic concentrations, with potent antileishmanic activity. Using physalin D to treat mice infected with Plasmodium burgdorferi can reduce parasitaemia and delay death, demonstrating its antimalarial activity against P. falciparum [96]. Among the five fractions (P1, P2, P3, P4, and P5) obtained by Yao [83], P2, P3, and P4 had inhibitory effects on the growth of Mycoplasma toxin, among which P2 and P3 had strong inhibitory effects. In conclusion, many experiments have shown that the multiple extracts of P. alkekengi have significant anti microbial effects, and the main active ingredients are physalins, physakengoses, and chlorogenic acid. Physalis alkekengi extracts have inhibitory effect on a variety of pathogenic bacteria and parasites and have a regulatory effect by inhibiting harmful bacteria while promoting beneficial bacteria. However, despite their potential, the specific mechanism of action of these extracts is rarely studied, and further research is needed.

4.3. Antioxidative effects

Oxidative stress damage is a common stress injury that predisposes an organism to ageing and various chronic diseases if excess oxygen free radicals are present. The aqueous extracts of the calyx of P. alkekengi can enhance the resistance of nematodes to oxidative stress by up-regulating the expression levels of the antioxidant genes gst-4, gst-7, sod-3, and hsp16.2 in nematodes, thereby delaying aging. In addition, the aqueous extract from P. alkekengi was proven to have significant antioxidative effects [97]. Furthermore, the aqueous extract of P. alkekengi can also prevent nonalcoholic fatty liver disease (NAFLD) in mice by reducing the malondialdehyde (MDA) content in the liver tissue of NAFLD model mice [98]. Pei et al. [99] found that n-hexane-acetone extracted from P. alkekengi can reduce the MDA content and increase the SOD and GSH-Px enzyme activities in aging rats induced by d-galactose, which can effectively enhance the antioxidant capacity of rats. It has been shown that both the leaf and fruit extracts of P. alkekengi showed inhibition of xanthine oxidase, which mainly contains total phenols, flavonoids, and carotenoids [100]. Additionally, Wu et al. [71] examined the scavenging ability of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and found that the antioxidant activity of the petroleum ether part of P. alkekengi fruit was superior to that of the calyx.

P. alkekengi polysaccharides have a strong scavenging ability against 2, 2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⁺), hydroxyl radical ('OH), superoxide anion (O₂⁻), and DPPH, and have significant antioxidant activity [[101], [102], [103]]. Li et al. [104] found that the calyx, stems, and leaves of P. alkekengi have stronger antioxidant activity by fluorescence recovery after photobleaching method, in which the total flavonoids of stems and calyx had stronger scavenging ability of against DPPH, and the total flavonoids of stems and fruits had stronger scavenging activity of against ABTS⁺. It has been shown that the total flavonoids from the calyx of P. alkekengi have the ability to scavenge oxygen radicals such as ABTS⁺, 'OH, O₂⁻, DPPH, and sodium nitrite (NaNO₂), and the scavenging ability is enhanced with increasing mass [105]. Zhang et al. [106] showed that physalin B could ameliorate oxidative stress by activating the P62–kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor-erythroid 2-related factor 2 (NRF2) antioxidant pathway to improve NAFLD. Huang et al. [107] used supercritical carbon dioxide extraction to recover carotenoids from the calyx of P. alkekengi and confirmed their antioxidant capacity using free radical scavenging activity tests. In conclusion, numerous studies have shown that P. alkekengi extracts have significant antioxidative effects, with the main active ingredients being polysaccharides and flavonoids. The mechanism of action is related to enhancing antioxidant gene expression, increasing antioxidant enzyme activity, enhancing resistance to oxidative stress, scavenging oxygen free radicals, thereby reducing oxidative stress damage. Therefore, the use of P. alkekengi extract as a natural antioxidant in health and care products and cosmetics has broad prospects for development and application.

4.4. Hypoglycaemic effects

Diabetes is a metabolic disease characterised by hyperglycaemia, and chronic damage to tissues and organs is easily caused by long-term hyperglycaemia. Both the aqueous and ethanol extracts of the calyx of P. alkekengi lowered blood glucose levels and increased glucose tolerance in streptozotocin (STZ)-induced diabetic rats, with the ethanol extract of the calyx of P. alkekengi having a more significant hypoglycaemic effect [108]. Zhang et al. [109] found that ethyl acetate extracted from P. alkekengi can improve glucolipid metabolism in high-fat diet combined with STZ-induced diabetic rats by stimulating glucose uptake and utilization. Hu et al. [110] found that ethyl acetate extracts of the above-ground parts and fruits of P. alkekengi could reduce cytochrome P450-2E1 expression, inhibit α-glucosidase, reduce oxidative stress, and enhance glucose transporter 4 (GLUT4) expression and insulin sensitivity, which showed antidiabetic activity both in vitro and in vivo.

Li et al. [111] elucidated the hypoglycaemic mechanism of P. alkekengi polysaccharides by establishing a mouse model of tetraoxonin-induced diabetes. The study demonstrated that P. alkekengi polysaccharides can repair and protect the pancreas and pancreatic islet cells to stimulate insulin secretion and lower blood glucose levels. They can also regulate liver glucose metabolism by increasing the synthesis of hepatic glycogen and the content of glucokinase and improve the disorder of glucose metabolism in diabetic mice, thus lowering blood glucose concentration. The molecular mechanism of action involves activation of the phosphatidylinositol-3-kinase (PI3K)/Akt insulin signalling pathway and upregulation of GLUT4, Akt, PI3K, and insulin receptor (InsR) mRNA, which are key molecules of the insulin signalling pathway. This further enhances the effect of insulin signalling, improving the sensitivity of the body to insulin, stimulating glucose transport, promoting the utilization and metabolism of sugar in peripheral tissues and target organs, thus lowering blood glucose. In addition, the steroidal saponins in the calyx of P. alkekengi can also reduce blood glucose concentrations and alleviate hyperglycaemic symptoms in tetraoxypyrimidine-induced diabetic mice [112]. Li et al. [113] found that the total steroidal saponins of P. alkekengi inhibited α-amylase in a dose-related manner and speculated that competitive reversible inhibition was involved. In addition, physalins in sterols inhibit both α-glucosidase and α-amylase, with more significant inhibition of α-amylase [114]. Wang [115] showed that the polyphenols in the fruits of P. alkekengi can also lower blood glucose by promoting the expression of glucokinase (GK), glucose transporter 4 (GLUT2), and pyruvate kinase (PK), inhibiting the expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), and stimulating key enzymes of glucose metabolism to regulate glucose metabolism in the livers of II-diabetic mice. Mezhlumyan et al. [116] showed that protein fractions in P. alkekengi also had high hypoglycaemic activity. In conclusion, a variety of compounds in P. alkekengi have hypoglycaemic effects, and their main active ingredients are polysaccharides, sterols, and polyphenols. The glucose-lowering mechanism of P. alkekengi extract is mainly related to the activation of the insulin signalling pathway, thereby enhancing insulin level and sensitivity, and hepatic glucose metabolising enzyme activity, and inhibiting glycoside and starch hydrolases, thus lowering blood glucose level. In recent years, the hypoglycaemic effect of P. alkekengi has been gradually emphasised, among which the hypoglycaemic effect of the calyx polysaccharides has been studied in greater detail. The significant hypoglycaemic activity of these polysaccharides demonstrated their potential for the development of a natural hypoglycaemic agent for application in pharmaceuticals and health products. Furthermore, the hypoglycaemic effect of the polyphenolic components of the fruit also provides scope for the development and application of P. alkekengi.

4.5. Analgesic effects

Pain is a subjective feeling of discomfort caused by damage to tissues in the body. Gong et al. [117] used various pain measurement methods to measure the pain response of mice after gavage with aqueous extract of P. alkekengi, indicating that the extract has an analgesic effect. In addition, studies have also shown that aqueous extracts and ethyl acetate sites from the calyx of P. alkekengi can also inhibit inflammation-induced pain [78,80]. After measuring the analgesic effect of physalin A using hot plate and torsion methods, Zhao et al. [118] used molecular docking techniques and found that physalin A might exert the analgesic effect by regulating leukotriene A-4 hydrolase (LTA₄H) enzyme activity in the arachidonic acid metabolic pathway. Therefore, physalins have been proposed as the active ingredient that generates this effect. Few studies on the analgesic effects of P. alkekengi have been conducted to date. However, the analgesic activity of natural medicine is characterised by few side effects, so P. alkekengi shows great clinical potential and warrants further research.

4.6. Immunomodulatory effects

Immunomodulation is a physiological function of the body that relies on the immune system to recognise and eliminate antigenic foreign substances and maintain its own physiological dynamic balance and relative stability. It has been shown that the soluble polysaccharides and calyx saponins of P. alkekengi significantly increased the antibody titres of anti-OVA-specific antibodies immunoglobulin G (IgG), immunoglobulin G1 (IgG1), and immunoglobulin G2b (IgG2b) in mouse anti-serum, significantly induced and promoted Th1 and Th2 cell-mediated humoral immune responses, thereby enhancing the cellular and humoral immune responses [119,120]. In addition, P. alkekengi fruit polysaccharides could bind to toll-like receptor 4, a surface receptor on mouse bone marrow dendritic cells to affect the immune function of bone marrow dendritic cells and promote initial T cell differentiation to Th1 and Th2 [121]. Yang et al. [122] co-immunised mice with water-soluble polysaccharides of P. alkekengi as a nucleic acid vaccine adjuvant, which significantly enhanced their immune response and laid the foundation for the development of P. alkekengi polysaccharides in vaccine adjuvants. In conclusion, the immunomodulatory effects of P. alkekengi are mainly attributable to its polysaccharides and saponins, and the mechanism of action may be related to promoting T cell differentiation and stimulating Th1 and Th2 immune responses.

4.7. Anti-tumour effects

Cancer is a serious threat to human life and health and causes millions of deaths worldwide every year. Most malignant tumours are treated clinically by surgical resection combined with radiotherapy, but both methods can cause serious irreversible damage to the body. Therefore, there is an urgent need for the research of natural drugs with anti-tumour activity and broad application prospects. It has been shown that the alcohol extract of P. alkekengi can effectively inhibit the proliferation and promote apoptosis of colon cancer cells [123]. The trichloromethane extract of P. alkekengi showed antiproliferative effects on HeLa, MCF-7, and A431 cell lines, with the fraction containing physalin D being the most active [124].

Steroids are the main active ingredients in the anti-tumour activity of P. alkekengi. Li et al. [35] found that steroids in P. alkekengi exhibited strong cytotoxicity against HeLa human cervical cancer, SMMC-7721 human hepatocellular carcinoma, and HL-60 human hepatocellular carcinoma tumour cell lines, with physalin B exhibiting the strongest cytotoxicity. Fu et al. [125] showed that physalins in sterols could enhance apoptosis in multiple myeloma cells by inhibiting signal transducers and activators of transcription 3 (STAT3) signalling pathway-induced expression of downstream target genes. He et al. [126] found that physalin A could selectively induce apoptosis in human fibrosarcoma HT1080 cells by activating the death receptor-related exogenous apoptotic pathway and upregulating the expression of caspase-3 and caspase-8, and physalin A had no growth inhibitory effect on normal cells. Physalin A can also inhibit cancer cell proliferation by participating in the p38 MAPK/reactive oxygen species (ROS) pathway to induce G2/M cell cycle block in human non-small cell lung cancer A549 cells, as well as inhibit tumour cell xenograft growth and promote apoptosis by inhibiting the janus kinase 2 (JAK2)/3-STAT3 signalling pathway [127,128]. Shin et al. [129] found that physalin A could also increase the expression of detoxifying enzymes by activating NRF2 and its target genes through the regulation of extracellular regulated protein kinases and p38 kinases in Hepa-1c1c7 and HepG2 hepatocellular carcinoma cells, thereby inhibiting cancer progression at the initial stages of carcinogenesis. Hao et al. [130] found that physalin A also induced iNOS expression and NO production in human melanoma A375-S2 cells, thereby inducing apoptosis and autophagy in A375-S2 cells. In addition, physalin A can also treat breast cancer through various pathways by increasing the mRNA expression level of the apoptosis-specific gene Bax, inducing autophagy in EGFR2 cancer cells, and inhibiting the Hedgehog and Hippo signalling pathways, cancer stem cell-specific genes, and mammosphere formation [[131], [132], [133]]. Wang et al. [134] showed that physalin B significantly reduced the activity of three human breast cancer cell lines: MCF-7, MDA-MB-231, and T-47D. The mechanism of action may be to induce cell cycle arrest in the G2/M phase in a p53-dependent manner and to promote the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, caspase-7, and caspase-9 to stimulate apoptosis. In addition, it has been shown that physalin B induced G2/M block and inhibited proliferation of human non-small cell lung cancer A549 cells by altering mitochondrial function through upregulating p21, and downregulating cyclin B1, cell division control protein cell cycle protein-dependent kinase 1 (CDK1) and oxidative phosphorylation multi-subunit activity [135]. Sun et al. [57] isolated withanolides from the calyx of P. alkekengi, in which withaphysalin B and a new withanolide compound exhibited strong cytotoxicity against A549 and K562 cell lines and induced apoptosis, with a possible mechanism of action through inhibition of the PI3K–Akt–mammalian target of rapamycin (mTOR) signalling pathway to exert anti-tumour effects.

Moreover, Ji [136] showed that luteoloside could block gastric cancer cells in S-phase by inhibiting the protein expression levels of the S-phase-related proteins cyclin-dependent kinase 2 (CDK2) and cyclin E1, inhibit the migration and invasion ability of gastric cancer cells, and up-regulate the protein expression of the apoptotic substrate PARP and the shedder of apoptotic core protein caspase-3, thereby regulating the apoptotic signalling pathway to promote apoptosis. This has the effect of promoting the ubiquitous degradation of mesenchymal-epithelial transition protein (MET) to inhibit the PI3K/Akt/mTOR pathway, which ultimately inhibits the proliferation, migration, and invasion of gastric cancer cells. In addition to this, Zhang et al. [85] also found that sesquiterpenoids have some cytotoxic properties. In conclusion, P. alkekengi has certain inhibitory effects on a variety of tumours, and its mechanism may be related to inducing G2/M phase arrest of cancer cells through various pathways to promote apoptosis and inhibit the proliferation of cancer cells. The main active ingredients of P. alkekengi with anti-tumour effects are steroidal compounds, especially the physalins, while the flavonoids and terpenoids in P. alkekengi also have anti-tumour activities. Therefore, the inhibitory effect of many types of cancer by various components of P. alkekengi demonstrates its potential as a prospective natural, anti-tumour medicine and warrants further research.

4.8. Anti-asthma effects

Asthma is a common multifactorial respiratory disease that is usually characterised by airway inflammation, immune cell aggregation, reversible airflow obstruction, and bronchial hyperresponsiveness. It has been shown that the methanol extract of P. alkekengi can inhibit airway hyperresponsiveness in ovalbumin (OVA)-induced asthmatic mice [137]. Bao [138] found that the aqueous extract of P. alkekengi can effectively reduce the total leukocyte count and eosinophil count in the blood of sensitised asthmatic mice, decrease the expression of interleukin-5 (IL-5) and interferon γ (IFN-γ) in lung tissue, selectively reduce the intensity of Th1 and Th2 expression in lung tissue, and reverse the imbalanced Th1/Th2 ratio. Liu et al. [139] found that different concentrations of P. alkekengi could significantly inhibit the release of histamine in the lung tissues of OVA-sensitised asthmatic mice, alleviate the inflammation of lung tissues of asthmatic mice, and reduce lung tissue damage, thus improving the symptoms of asthmatic mice and prolonging the latency period of asthma induction. Furthermore, Wu [140] showed that flavonols in P. alkekengi could activate the Nrf2-regulated defence system and are effective components in the treatment of respiratory diseases. In conclusion, the extracts of P. alkekengi have an anti-asthma effect, with flavonoids being the likely active ingredients contributing to this effect, and the mechanism of action may be related to reducing the expression of IL-5 and IFN-γ. Since the symptoms associated with asthma are related to inflammation and the immune system, the mechanisms of anti-asthmatic effect of P. alkekengi are also related to its anti-inflammatory and immunomodulatory effects.

4.9. Other effects

Furthermore, P. alkekengi has been shown have hypolipidemic, diuretic, vasodilatory, nephroprotective, and antifertility effects. Dong et al. [141] investigated the hypolipidemic effects of the aqueous and alcohol extracts of the calyx and fruit of P. alkekengi by establishing a hyperlipidaemic rat model and noted that the extracts of P. alkekengi were all effective in preventing hyperlipidaemia, with the aqueous extract of the calyx having the best therapeutic effect. Experimental results by Yang [27] showed that the diuretic effect of the calyx of P. alkekengi is not only related to its glycolic acid content, but also to the high potassium and magnesium content of P. alkekengi. Liu et al. [142] found that the aqueous extracts of P. alkekengi inhibited calcium inflow and the protein kinase C (PKC) signalling pathway, thereby relaxing phenylephrine and potassium chloride-induced vasoconstriction in a concentration- and non-endothelium-dependent manner in rat thoracic aorta. Ashtiyani et al. [143] showed that alcohol extracts from P. alkekengi could reduce urea nitrogen, serum creatinine, and sodium/potassium levels elevated due to cisplatin, thereby improving cisplatin-induced nephrotoxicity. Vessal et al. [144] found that aqueous extracts of the fruit and calyx of P. alkekengi can reduce progesterone levels and time-dependently inhibit the activity of the uterine creatine kinase BB-isoenzyme in mothers, thereby reducing the birth rate of pups and producing a antifertility effect.

5. Conclusions and future perspectives

This paper reviews the phylogenetic origin, chemical composition, pharmacological effects, and mechanism of action of P. alkekengi. More than 530 chemical components have been isolated and identified in P. alkekengi, mainly including steroids, flavonoids, alkaloids, volatile oils, polysaccharides, and other components. Among these, steroids, flavonoids, and volatile oils account for the largest proportion of components. However, volatile oils evaporate easily and are not suitable medicinal components; therefore, little research has been conducted on these oils. Among the sterols, the most researched components are the physalins, which are unique to Physalis L. A large number of pharmacological studies have demonstrated the anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, immunomodulatory, anti-tumour, and anti-asthma effects and their mechanisms of action in P. alkekengi. In addition, its diuretic, hypolipidemic, vasodilatory, nephroprotective, and antifertility activities have also been demonstrated, providing a theoretical basis for its use in clinical settings and as a health food. Among them, the main focus is on its anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, and anti-tumour effects. Combined with phytochemical and pharmacological analysis, steroids, flavonoids, and polysaccharides are the main active ingredients of P. alkekengi. Among these, physalins are the main active ingredients contributing to the anti-inflammatory, anti microbial, analgesic, anti-tumour, and antioxidative effects of P. alkekengi. The flavonoids mainly contribute to the anti-inflammatory, antioxidative, anti-tumour, and anti-asthma effects, and the polysaccharides mainly contribute to the antioxidative, hypoglycaemic, and immunomodulatory effects of P. alkekengi. As a natural medicine unique to the northeast region of China, P. alkekengi is cheap, widely cultivated, rich in resources, and has a variety and high content of pharmacologically active ingredients, most notably physalins. Therefore, P. alkekengi is highly valuable and warrants further in-depth research.

Although P. alkekengi and its active ingredients have been used in the treatment of several diseases and have been extensively studied pharmacologically in animal studies, the conclusions of these studies are still limited.

Although scholars at home and abroad have done a lot of research on P. alkekengi, there are still some problems to be solved. First, the pharmacological mechanisms of action of the anti microbial, analgesic, diuretic, and hypolipidemic effects are still unclear, and the conformational relationship of many pharmacological activities at the level of animal models, metabolomics, and macro-genomics of intestinal microflora is also less studied and warrants further in-depth research. Second, there are more studies on fruits and calyx, but few studies on roots, stems and leaves. These organs also contain medicinal components and therefore warrant further research. Third, because P. alkekengi appears mostly in the north-eastern region of China and is rare in other regions, it is not widely used as a food and health product, and research progress is slow. Fourth, although P. alkekengi showed good activity in both in vivo and ex vivo models, further confirmation of its effective use and possible clinical application is needed. In summary, as a natural medicinal and dual-use plant with a variety of functional properties, the development of related products has great potential and development prospects.

Author contribution statement

All authors listed have significantly contributed to the development and the writing of this article.

Data availability statement

No data was used for the research described in the article.

Funding

This research was supported by the Central Support for Local Universities Reform and Development Funds for Talent Training Projects (Key Technology and Product Creation for the Discovery of Quality Markers of Ganoderma Lucidum , an Authentic Medicinal Herb of Longjiang); the University Nursing Program for Young Scholars With Creative Talents in Heilongjiang Province (grant number UNPYSCT-2020219); the Science and Technology Innovation Talent Project of the Harbin Science and Technology Bureau (grant number CXRC20221106324); and the Harbin University of Commerce Research Support Program for doctor (grant number 22BQ02).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.