Table 4.
Biological activity and mechanism of action of Hawthorn.
| Extracts or Compounds | Observation or Methods | Effects | References | |
|---|---|---|---|---|
| Anticancer activity | ||||
| Triterpenoids isolated from hawthorn berries | In vitro, MTT assay. | All 15 triterpenoids showed effective antiproliferative activity against human HepG2, MCF-7 and MDA-MB- 231 tumor cells showed potent anti-proliferative activity(compound 2–4 EC50 < 5 µM). |
[111] | |
| Ursolic acid, oleanolic acid, corosolic acid, and maslinic acid | In vitro. | CA showed the highest antiproliferative activity against human HepG2 (EC50 = 9.44 μM), MCF-7 (EC50 = 22.01 µM) and MDA-MB-231 (EC50 =26.83 μM) tumor cells among the four triterpenoids, followed by UA, MA, and OA. |
[44] | |
| Phenylpropanoids isolated from hawthorn fruit | In vitro, MTT assay. | Five compounds (1a/1b, 2–4) were used in the treatment of human HepG2 and Hep3B cells with better cytotoxicity(1a IC50: 59.57, >100 µM; 1b IC50: 35.37, 70.42 µM; 2 IC50: 27.36, 39.40 µM; 3 IC50: 18.68, 38.96 µM;4 IC50: 17.50, 43.58 µM;). | [112] | |
| Homogeneous polysaccharide (HPS) | In vitro, WST-1 colorimetric method. | Treatments with 500 and 1000 μg/mL of HPS for 12 h resulted in more than 74% of growth inhibition against human HCT116 cell. | [49] | |
| An extract enriched with TOF | In vivo. | TOF extract from hawthorn leaves exerts an antitumor effect by decreasing the melanoma tumor growth in vivo (6 times less weight). | [55] | |
| Maslinic acid | In vitro, AO/EB staining assay and Annexin V/PI dual staining. | It can cause human neuroblastoma SHSY-5Y cells increase the percentage of apoptotic cells from 9% in the control group to 54% at higher drug doses. | [18] | |
| Cardiovascular system activities | ||||
| Hawthorn Leaf Flavonoids(HLF) | In vivo. | HLF protect against diabetes-induced cardiomyopathy in rats via PKC-α signaling pathway. | [25] | |
| Hawthorn Leafs Extract | In vitro, MTS. | Hydroalcoholic extracts of hawthorn leaves at 300 and 1000 mg/mL significantly reduced the frequency of arrhythmias induced by adrenaline stimulation. | [82] | |
| Hawthorn Fruit Extract (HFE) |
In vivo. | HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis. | [113] | |
| Flavonoids | In vivo, carrageenan-induced tail thrombosis model. |
Inhibiting TXA2 release, decreasing the level of Ca2+ in platelets or blocking glycoprotein IIb/IIIa receptors may be the mechanism of the antithrombotic effects of flavonoids. | [81] | |
| Hawthorn Fruit Extract | In vivo, Western Blot. | The hepatic triglyceride (TG) and malondialdehyde (MDA) levels were significantly reduced in the hawthorn groups compared with the ovariectomized group (p < 0.05). | [83] | |
| Hawthorn Fruit Extract | In vivo, spectrophotometry. | Compared with the blood TC levels of rats in the type 2 diabetic group, the blood TC levels of rats in the high, medium and low dose of Hawthorn extract decreased by 162.54%, 122.68% and 92.13% respectively. | [86] | |
| Hawthorn Fruit Extract | In vivo. | Echocardiographic parameters (LVESD, LVEDD) were reduced in rats with chronic heart failure treated with hawthorn extract (p < 0.01) | [84] | |
| Hawthorn Extract | In vivo. | Hawthorn extract groups suppressed the high-fat diet-induced increases in the concentrations of LDL (p < 0.05). | [85] | |
| Anti-hyperglycemic activity | ||||
| Hawthorn Fruit Extract | In vivo. | Hawthorn extract in high, middle and low dose could significantly reduce the fasting blood glucose levels of type II diabetic rats from 20.25 ± 1.9 mmol L−1 to 10.5 ± 0.87 mmol L −1, 15.13 ± 0.55 mmol L −1 and 17.9 ± 0.87 mmol L−1 (p < 0.01 and p < 0.05). | [86] | |
| Hawthorn polyphenols, D- chiro- inositol (DCI), and epigallocatechin gallate (EGCG) |
In vitro. | Three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. | [95] | |
| Hawthorn Extract | In vivo. | Hawthorn treated groups (0.5 g/kg/day, 1.0 g/kg/day) showed a significant reduction in insulin resistance compared with the HF group (p < 0.05, p < 0.01). | [85] | |
| Antibacterial and anti-inflammatory activities | ||||
| Hawthorn Fruit Extract | In vivo. | The hawthorn treatment group reduced the levels of IL-6, IL-8, IL-1β and TNF-α in cardiomyocytes due to doxorubicin treatment for heart failure (p < 0.01). | [93] | |
| Water fraction from hawthorn fruit | In vitro, ELISA. | Water fraction from hawthorn fruit at 200, 400 and 600 µg/mL increased the survival rate of RAW264.7 cells to 61.8%, 72.7% and 83.4% respectively. | [99] | |
| Hawthorn Methanolic Extract (ME) | In vitro. | ME from hawthorn had a minimum MIC and MBC value of 1.25 µg/mL against S. aureus and S. typhimurium. | [38] | |
| Hawthorn polysaccharide (HAW1-2) | In vivo. | The relative expression of IL-1β, IL-6 and TNF-α were suppressed after HAW1–2 treatment. | [50] | |
| Hawthorn phenolic extract | In vivo. | The extract decreased the percent-age of CD4−CD8− and CD4+ thymocytes but elevated the percentage of CD4+CD8+ and CD8+ thymic cells, increased the total number, percentage, and absolute count of T and B splenocytes. | [75] | |
| Pectin oligosaccharide (POS) | In vivo, ELISA. | Higher dose (0.75, 1.5 g/kg) of POS significantly (p < 0.01) decreased the contents of hepatic TNF-α and IL-6, while significantly (p < 0.05–0.01) increased the level of IL-10, compared with the high fat control group. | [98] | |
| Total Flavonoid Extract from Hawthorn (TFH) | In vitro. | TFH (50–200 µg/mL) treatment inhibited the increase of inflammatory cytokines IL-6, IL-1β, MCP-1 and IL-8 in Caco-2 cells in a dose-dependent manner. | [76] | |
| Anti-digestion activty | ||||
| Hawthorn Seed Eextract (HSEAE) | In vivo. ELISA. | Different doses of HSEAE effectively promoted the gastric emptying and small intestinal propulsion (p < 0.05 or p < 0.01). In addition, HSEAE increased SOD and GSH-Px in the rats’ stomachs while decreasing MDA, and increased plasma ghrelin while decreasing MTL and GAS (p < 0.05 or p < 0.01). | [104] | |
| Ethyl acetate part of hawthorn | In vivo, LC-MS. | The effect of ethyl acetate extract of hawthorn on gastric emptying rate and intestinal propulsion rate in a rat model of atropine sulfate-induced gastrointestinal motility retardation was significant (p < 0.05, p < 0.001). | [92] | |
| Charred hawthorn | In vivo. | Hawthorn decoction coupled with the odor of charred hawthorn effectively alleviate high-calorie-diet-induced dys-pepsia in rats by regulating the “Brain-Gut” axis and gut flora. | [91] | |
| Antioxidant activity | ||||
| Triterpenoids isolated from hawthorn berries | In vitro, PSC and superoxide anion free radical assay. | In PSC assay, compounds 1, 10 and 12 had pronounced antioxidant activity with an EC50 of 0.2 ± 0.01, 0.5 ± 0.01, and 0.7 ± 0.01 µM. | [111] | |
| Phenolic composition of Kazakh Crataegus | LC-MS | In the free radical scavenging activity assay (DPPH), the most potent extract was the phenolic compound from hawthorn leaves (IC50 48 ± 2 µg/mL). | [20] | |
| Hawthorn polyphenol extract (HPE) | In vivo and vitro, MTT. | After UVB irradiation, the cell viability significantly decreased (p < 0.05). HPE at 5 and 10 µg/mL significantly increased cell survival (p < 0.05). | [102] | |
| Phenolic compounds | In vitro, ORAC. | The antioxidant activity of phenolic compounds in hawthorn was significant, with ORAC values for the eight phenolic compounds ranging from 5.25 ± 0.54–62.79 ± 1.46 μmol TE/μmol. | [114] | |
| Hawthorn fruit extract | FRAP. | The antioxidant activity was widely varied (p < 0.001) in species of Crataegus, ranging from 0.32–1.84 mmol Fe++/g DW. | [12] | |
| Phenolic compounds | DPPH, ABTS, and FRAP. | The total antioxidant activity of organic fresh hawthorn berry fruit determined by DPPH, FRAP and ABTS assay was up to 286 ± 4, 320 ± 5 and 328 ± 6 μmol TE/g DW. | [54] | |
| Hawthorn extract | DPPH. | The DPPH scavenging capacity of the fresh hawthorn slices was 3.48 mmol TE/100 g DW. | [101] | |
| Extract from peel of hawthorn fruit(EPHF) |
DPPH and ORAC. | EPHF has the strongest oxygen radical scavenging capacity (IC50 = 11.72 μg/mL). | [115] | |
| Organic freeze-dried hawthorn berries (OFDHB) | ABTS, FRAP and DPPH. | The peel of OFDHB sample had the highest antioxidant capacity followed the decreasing order of ABTS (577.5 µmol TE g−1) > FRAP (455.84 µmol TE g−1) > DPPH (410.75 µmol TE g−1) assay. | [4] | |
| Flavonoids | FRAP. | The highest antioxidant activity was observed in the leaves of C. pentagyna as 4.65 mmol Fe++/g DW, whereas the lowest activity (0.9 mmol Fe++/g DW) was found in the leaves of C. azarolus var. aronia. | [116] | |
PSC: peroxyl radical scavenging capacity; MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay; ELISA: enzyme-linked immunosorbent assay; ORAC: oxygenradical absorbance capacity; DPPH: 1,1-diphenyl-2-picrylhydrazyl; FRAP: ferric-reducing antioxidant Power; ABTS: Total Antioxidant Capacity Assay Kit with ABTS method; 1a/1b, 2–4: (+)-crataegusanoid A, (−)-crataegusanoid A, crataegusanoid B, crataegusanoid C, crataegusanoid D.