Table 10.

Summary of biological activities of Zanthoxylum species.

Plant Species and Part Used	Test Substance	Results	Refs.
Antioxidant properties
Z. budrunga seeds	Polyphenol-rich crude ethanol extract	Good DPPH radical scavenging effect (IC50 value of 82.60 μg/mL) compared to ascorbic acid (IC50 value of 12.58 μg/mL) and ferric reducing power relative to ascorbic acid standard	[179]
Z. bungeanum pericarp and seed	Magnoflorine and arbutin isolated from them	Magnoflorine and arbutin showed weak antioxidant activities	[125]
Z. bungeanum fruit	Hyperoside and quercitrin isolated from the fruit	Strong antioxidant and radical scavenging activities	[133]
Z. armatum leaves	Essential oil	Good DPPH radical scavenging activity (IC50 = 27 μg/mL) relative to ascorbic acid (IC50 = 15.0 μg/mL)	[123]
Z. armatum leaves	crude methanol extract, Essential oil and ethyl acetate fraction of the crude extract	Radical scavenging, ferric reducing and divalent metal chelating potentials	[85]
Z. zanthoxyloides fruits, leaves, stems, trunk barks, and root barks	methanol extract	High radical scavenging and ferric reducing properties	[103,180]
Z. capense leaves	Acetone extract	Good antioxidant and radical scavenging activities	[19]
Z. syncarpum Tull. Branches	crude ethanol extract, its alkaloidal fraction and 4-(methylamino)-benzoic acid isolated from it	The crude extract and its alkaloidal fraction inhibited DPPH radical scavenging activities with IC50 values of 140.29 μg/mL and 56.17 μg/mL, respectively relative to quercetin (IC50 = 4.77 μg/mL). The crude extract, the alkaloidal fraction and 4-(methylamino)-benzoic acid potently inhibited hydrochloric acid-induced corrosion; 4-(methylamino)-benzoic acid showed the best corrosion inhibition	[135]
Z. leprieurii stem bark	hydroethanol and aqueous	Good antioxidant activity	[15]
Anti-diabetic effects
Z. chalybeum stem bark and root bark	Aqueous extract	Hypoglycemic activity and protected β-cells from damage	[155,157]
Z. armatum bark	Aqueous-ethanol extract	Anti-diabetic and hypoglycemic activities	[162]
Z. zanthoxyloides leaves	Dietary formulation	Exhibited good anti-diabetic, hepatoprotective and hypolipidemic effects against alloxan toxixity in rats	[196]
Z. armatum leaves	Aqueous extract	Hypoglycemic and inhibition of lipase, α-amylase and α/β-glucosidases activities	[160]
Z. armatum fruits, bark and leaves	methanol extract	Suppressed glucose level, increased insulin secretion via KATP channel and inhibited β-glucosidases activities (94% by bark extract, 97% by leaf extract and 84% by fruits extract	[161]
Gatro-protective effects
Z. zanthxyloides root bark	Ethanol extract	Inhibited ulcer index by 71% and 85% at 250 and 500 mg/kg via inhibition of cholinergic, nicotinic and histaminic receptors	[135]
Z. nitidum stem bark	aqueous extract	inhibited ulcer by 31% and 55% at 100 and 200 mg/kg by inhibiting gastric secretion	[170]
Z. nitidum roots, stems and leaves	Aqueous extracts and total alkaloid extract	gastroprotective effect by increasing NO, prostaglandin E2 and antioxidant status as well as reducing lipid peroxidation	[55]
Z. nitidum root	aqueous extract	Inhibition of gastric acid secretion and cytotoxic against H. pylori by inhibiting its urease activity	[56]
Z. rhoifolium stem barks	ethanol extract	Antiulcer activity by antioxidant protection of the mucosa from free radical-mediated oxidation, activation of KATP channel and increase in NO availability	[173]
Hepatoprotective effects
Z. bungeanum fruits	Glycoprotein	Hepatoprotective properties by mechanisms related to anti-oxidative and radical scavenging properties	[63]
Z. bungeanum leaves	crude methanol extract	Hepatoprotective properties by antioxidant activity and inhibition of lipid peroxidation and aniline hydroxylase activity	[174]
Z. armatum leaves	crude methanol extract	Inhibited hepatic damage by antioxidant mechanism	[86,175]
Z. armatum fruit	aqueous extract	Protected liver cells from damage by antioxidant status elevating catalase and vitamin C levels in serum and non-protein thiols in liver homogenate and lowering of malondialdehyde and liver enzyme levels in serum	[177]
Lipid-lowering effects
Z. bungeanum fruit and pericarp	petroleum ether, Crude ethanol extract, ethyl acetate and n-butanol fractions	Hypolipidemic activity by inhibiting in vivo lipid synthesis and increasing breakdown	[118,178]
Z. bungeanum fruit	Ethanol extract	Inhibited lipid synthesis, transport and storage in both 3T3-L1 adipocytes and high fat diet-induced obese mouse	[179]
Z. heitzii stem bark	aqueous extract	Reduced lipid levels by lipid synthesis inhibition and increasing the breakdown, protected cells from hyperlipidemia damages	[89]
Anti-hypertensive effects
Z. bungeanum leaves	crude methanol extract and its aqueous, n-hexane, ethyl acetate and n-butanol fractions	Induced vasorelaxation of smooth muscles by acting through SOCC- and Akt-eNOS-sGC-cGMP signaling in isolated aorta	[208]
Z. gilletii stem barks	aqueous extacts	Reduced systolic and diastolic blood pressures, pulse pressure and heart rate by over 75% through NO signaling	[51,148]
Cardioprotective effects
Z. acanthopodium fruit	ethyl acetate extract	Protected the myocardium from doxorubicin-generated cardiac damage	[140]
Z. bungeanum fruits	crude aqueous and alcoholic extracts and hydroxy-α-sanshool, hydroxy-β-sanshool, xanthoxylin, mikanin, hyperin, isoquercitrin, rutin, myricetin, myricitrin, quercitrin and isovanillic acid isolated from them	Improved breathing rate in cultured cardiac cells by inducing calcium uptake and modulating sarcoplasmic reticulum Na+/K+- and Ca2+-ATPase activities	[125]
Z. chalybeum root bark	aqueous extract	Attenuated diabetes-related myocardial dysfunction	[157,190]
Neuro-protective and Alzheimer′s disease modulatory effects
Z. bungeanum pericarps	crude extract and alkylamides isolated from it	Potent neuritogenic activity	[126]
Z. capense root	methanol and ethyl acetate extracts	Inhibition of rotenone-elicited neuronal injury in SH-SY5Y neuroblastoma cells	[151]
Z. bungeanum leaves	crude methanol extract and flavonoid-rich fraction	Good antioxidant and radical scavenging activities and Strongly inhibited hydrogen peroxide-induced neuronal cell damage in neuronal PC12 cells	[127]
Z. heitzii fruits and barks	syringic acid isolated from them	Potent neuroprotective activity against ischaemia/reperfusion (OGD/R) neuronal injury	[153]
Z. schreberi bark	Crude extract and berberine, chelerythrine and columbamine from it	Strongly inhibited acetylcholinesterase and butyrylcholinesterase	[11]
Z. monophylum bark	Crude extract and berberine, chelerythrine and columbamine isolated from it	Strongly inhibited acetylcholinesterase and butyrylcholinesterase	[11]
Anti-inflammatory and antinociceptive effects
Z. austrosinense root	Alkaloids isolated from ethanol extract	Strongly inhibited NO production in LPS-activated mouse macrophage RAW 264.7 cells (IC50 values = 0.89–9.62 μM)	[114]
Z. budrunga seeds	crude ethanol extract	The extract at 250 and 500 mg/kg inhibited acetic acid-induced writhings in mice by 65.28% and 74.30%, respectively relative to 81.95% inhibition by diclofenac sodium that served as standard. Similarly, the extract at the same doses time and dose-dependently inhibited hot plate induced pain at latency time slightly lower than morphine that served as standard.	[203]
Z. capense leaves	Acetone extract	Good anti-inflammatory activity by inhibiting 15-lipoxygenase activity in vitro and suppressed nitric oxide synthesis in activated RAW 264.7 macrophage by 33–86% at 3.12–32 μg/mL	[11]
Z. zanthoxyloides root	aqueous extract	Strongly inhibited proteases and membrane damage induced by hypotonic solution	[195]
Z. armatum roots and stems	Ethanol extract and ethyl acetate fraction	Demonstrated good anti-inflammatory activities against several models of inflammation	[198]
Z. nitidum root and stem	Methanol extract	Suppressed feeling of both acute and chronic pain as well as inhibited both acute and chronic inflammation in both in vivo and in vitro models	[119]
Z. rhetsa stem bark	methanol extract	Moderately inhibited acetic acid-generated writhings in mice by 47.82% and 58.89% at 250 and 500 mg/kg, respectively compared to 67.30% by reference drug, aspirin at 100 mg/kg	[202]
Z. budrunga root bark	ethanol extract	At 250 and 500 mg/kg doses, the ethanol extract significantly increased the latency time of response to hot plate induced pain (5.80 and 6.81 s) relative to control (3.29 s) and morphine (9.60 s). The extract potently inhibited acetic acid-provoked writhings in mice by 64.58% and 77.43% at 250 and 500 mg/kg, respectively relative to 81.9% by diclofenac sodium	[203]
Z. bungeanum pericarps	ethanol extract and amides isolated from it	Good anti-inflammatory activities by inhibiting NO production by LPS-stimulated RAW264.7 macrophages	[124,197,198,199,200,201,202,203,204,205,206,207,208],
Anti-asthmatic effect
Z. bungeanum seed	Essential oil	Inhibited nitric oxide production and suppressed pulmonary injury and infiltrations of inflammatory cells by inhibiting protein level and gene expression of inflammatory mediators and their receptors	[209]
Anti-arthritic effects
different parts of Z. bungeanum	Ethanol extract	Inhibited monosodium idoacetate-induced osteoarthritic inflammation and pain as follows: stalks (65%), roots (11.8%), twigs (84.7%), fruits (72.8%) and leaves (91.6%) through inhibition of protein level and mRNA expression of iNOS and COX-2	[201]
Z. bungeanum cake	Z. bungeanum-cake-separated moxibustion	Inhibited Freund’s complete adjuvant-induced rheumatoid arthritis by preventing edema formation, histological markers of inflammatory damages to the tissues and levels of pro-inflammatory cytokines (IL-1β and TNF-α) in serum	[63]
Anti-thrombotic effect
Z. schinifolium bark	Coumarins, alkaloids and triterpenoids isolated from chloroform fraction	Significantly inhibited platelet aggregatory response	[179]
Z. schinifolium root bark	Extract and 30 isolated compounds	Significantly inhibited collagen, arachidonic acid and platelet-activating factor-induced platelet aggregation	[122]
Z. nitidum var. tomentosum roots	Ethanol extract and toddalolactone isolated from it	Strongly inhibited PAI-1 and PAI-1-induced clot formation and induced breakdown of preformed clot in vitro. toddalolactone also inhibited ferric chloride-generated clot formation and hepatic necrosis and increased bleeding time in mice	[13]
Anti-spasmodic effect
Z. fagara stem bark	Crude ethanol extract	Suppressed muscle spasm and modulate muscle tone and contraction in isolated rat ileum, in vitro	[114]
Z. armatum fruit, bark and leaves	Methanol extract	Inhibited butyryl cholineesterase activity by 51%, 83% and 38%, respectively and potently relaxed precontracted rabbit jejunum strips, intestine, trachea and thoracic aortic rings	[207]
Z. rhoifolium leaves	alcoholic and aqueous extracts	Suppressed muscle spasm and modulate muscle tone and contraction in isolated rabbit duodenum, in vitro	[208]
Oesteoprotective effect
Z. piperitum fruit	Aqueous-ethanol extract	Exerted osteoprotective effects by inhibited the activation of c-fos/NFATc1/NF-κB pathway in osteoclast of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoporosis in ovariectomized mice	[210]