Table 4.
Biological activities of Annona squamosa L. leave extracts.
| Variety | Type of Extract | Bioactive Compounds Identified | Type of Cell Lines/Type of Study | Major Findings and Molecular Mechanisms of Action | References |
|---|---|---|---|---|---|
| Anti-cancer activities | |||||
| Leaves were obtained from a local plant nursery in Ta’if City, Saudi Arabia | Methanolic and acetonic extracts | Phenolics, annonaceous acetogenins, saponins, flavonoids, alkaloids, glycosides, alkaloids, steroids, and terpenoids | MCF-7 and MDA-MB-231 breast cancer cell lines | 100 µg/mL extract decreases cell viability and reduced their proliferation to ~60%. | [62] |
| Leaves were obtained from botanical garden in Narsapur, W.G.Dt, South India | Extracts prepared using double distilled water | NA | HeLa (cervical) cancer cell line | IC50 value against HeLa cells was estimated to be 25 μg/mL. | [67] |
| Leaves were obtained from Lumajang Regency, East Java, Indonesia. | Ethanolic extract | 12,15-cis-squamostatin-A, bullatacin | Human colon cancer cell lines (WiDr) | IC50 value against WiDr cells was estimated to be 292.39 µg/mL. | [68] |
| Leaves were obtained from department of Pharmacognosy, Faculty of Pharmacy, University of Karachi, Pakistan | Ethanolic extract | Annoreticuin and Isoannoreticuin | Colon cancer cell line (HCT-116), breast carcinoma cell line (MDA-MB-435), prostatic cancer cell line (DU145), human epidermoid carcinoma cell line (KB-3-1), lung cancer line (H460), and hepatocellular carcinoma cell line (BEL7404) | IC50 values of 13.66 µg/mL for KB 3-1 cells, 1.37 µg/mL for HCT-116 cells, 74.51 µg/mL for HEK293 cells, 53.86 µg/mL for KB-3-1 cells, and 15.06 µg/mL for HCT-116 cells. | [55] |
| Anti-diabetic activity | |||||
| ASLs were collected from IARI, New Delhi, India | Ethanolic extract | In vivo (Wistar strain of rats with alloxan (80 mg/kg) and STZ (50 mg/kg i.p.) induced diabetes) |
Administration of ASLs extract (350 mg/kg), significantly reduced the FBG by 6%, 26.8%, and 13% in normal, alloxan-induced, and STZ induces diabetic rats, respectively, and improved the glucose tolerance in diabetic rats. ASL also reduced TC (by 49.3%), LDL (by 71.9%), and TG (by 28.7%) and increased HDL (by 30.3%) in severely diabetic mouse. |
[69] | |
| Young ASLs were collected from Painkulam village, Tamil Nadu, India. | 95% Ethanol extract | In vivo (Wister male albino rats with STZ (65 mg/kg i.p.) induced diabetes) |
Administration of ASLs extract (250 mg/kg and 500 mg/kg) exhibited a significant reduction of FBG and increased the insulin level. | [70] | |
| ASLs | Hexane extract | In vitro (L6 Myotubes) and in vivo (Ob/ob mice modal) |
ASLs hexane extract (500 mg/kg b.i.d. p.o.) improved the glucose uptake, stimulated the IR-β and IRS-1 phosphorylation, and promoted the upregulation of mRNA (GLUT4 and PI3 kinase) in L6 myotubes. ASLs hexane extract inhibited the PTP1B with an IC50 17.4 µg/mL Oral administration of ASL hexane extract significantly declined random glucose (27.7%) and TG (30.5%). |
[51] | |
| ASLs | Water extract, Hexane extract, and methanol extract | In vivo (CF strain rats) | Hexane extract inhibited the α-glucosidase (75.69 ± 1.7%) in comparison to acarbose (53.60 ± 1.45%) Hexane extract (100 mg/kg and 400 mg/kg) improved insulin level (11.58 ± 1.8 µU/mL and 16.28 ± 1.2 µU/mL) and reduced BGL (41.18 ± 2.46% and 78.10 ± 1.57%), respectively. |
[52] | |
| Young ASLs were collected from the Regional Research Institute of Unani Medicine, Aligarh, India. | Aqueous extract | In vivo (male albino Wister rats with STZ (55 mg/kg i.p.) induced diabetes) | Oral administration of ASLs extract (300 mg/kg) significantly reduced the BGL, lipid peroxidation and also increased the activity of the antioxidant enzymes. | [71] | |
| ASLs collected from Kolli Hills, Tamil Nadu, India | 95% ethanol extract | In vivo (male albino Wister rats with STZ (50 mg/kg i.p.) induced diabetes) | ASLs extract (100 mg/kg) significantly reduced BGL, glycosylated hemoglobin, creatinine, and urea. | [72] | |
| ASLs were collected from IARI, New Delhi, India | Water extract | In vivo (Albino Wister rats with STZ (50 mg/kg i.p.) induced diabetes) | ASLs extract (350 mg/kg) significantly improved the lipid profile and increased the activities of antioxidant enzymes. | [66] | |
| ASLs were collected locally, Indore, India. | 80% Methanol | Quercetin-3-O-glucoside | In vivo (Wistar male rats with alloxan monohydrate (120 mg/kg i.p.) induced diabetes) |
Quercetin-3-O-glucoside (15 mg/kg p.o.) significantly increased serum insulin, decreased glucose, reduced oxidation of lipid (p < 0.001), and increased antioxidant enzyme activity (p < 0.001). | [49] |
| Antioxidant activities | |||||
| ASLs, Rajshahi, Bangladesh | Methanol extracts | Phenols and flavonoids | In vitro | IC50 of 7.81 ± 0.1 μg·mL−1 for DPPH, IC50 of 29.60 ± 0.17 (μM of Trolox for oxygen radical absorbance capacity (ORAC). |
[73] |
| ASLs, Tamil Nadu, India | Ethanol extracts | Flavonoids | In vitro | IC50 of DPPH, ABTS, superoxide dismutase, nitric oxide, and lipid peroxidation were found to be 110, 40, 115, 60, and 955 μg·mL−1, respectively. | [74] |
| ASLs, Andhra Pradesh, India | Ethanol extracts | Flavones | In vitro | % DPPH radical scavenging was 45.62 at 100 (μg·mL−1) concentration. |
[60] |
| ASLs, Egypt | Methanol 80%, acetone 50%, ethanol 50%, and boiling water. | Phenols | In vitro | Total antioxidant activity was reported highest in acetone extract i.e., 1625.38 ± 68.55 ascorbic acid/g of extract, and lowest in case of water 639.65 ± 22.17 ascorbic acid/g of extract. | [3] |
| Anti-microbial activities | |||||
| Leaf Extract (India) |
Control (1 mL of 2% Gum acacia) | Steroids Alkaloids Glycosides Saponin Flavonoid Tannin Triterpenoid |
Antibacterial activity and measurement of wound healing activity of ASLs extract in Albino wistar rats. | Period of epithelisation—25 days | [61] |
| Petroleum ether | Zone of inhibition—19–22 mm at MIC-200 mg/ 0.1 mL. On addition of 300 mg/ kg (ED50 value) petroleum ether extract, wound healing induced within 16 days. |
||||
| Chloroform-water | Zone of inhibition- 19–21 mm at MIC-200 mg/ 0.1 mL. On addition of 300 mg/kg (ED50 value) chloroform-water extract, wound healing induced within 19 days. |
||||
| Alcohol | Zone of inhibition- 18–20 mm at MIC-200 mg/ 0.1 mL. On addition of 300 mg/ kg alcoholic extract, wound healing induced within 18 days. |
||||
| ASLs extract (Egypt) | Methanol 80% | Carbohydrates, tannins, phenolic compounds, polyphenols, and flavonoids |
Antibacterial activity of ASLs extracts using disc-diffusion method against six bacterial species. | Zone of inhibition diameter: 12–13 mm with 38–43% inhibition. | [3] |
| Acetone 50% | Zone of inhibition diameter: 14–16 mm with 41–51% inhibition. | ||||
| Ethanol 50% | Zone of inhibition diameter: 12–14 mm with 35–48% inhibition. | ||||
| Boiling water | Zone of inhibition diameter: 9–11 mm with 28–36% inhibition. | ||||
| ASLs extract (India) | Ethanol extract 25% 50% 75% 100% |
Polyphenols tannins, and terpenoids |
Estimation of the effect of ASLs extract on inhibition of six bacterial species | Zone of inhibition (in mm) 8–15 mm 10–17 mm 13–19 mm 15–22 mm |
[74] |
| Hepato-protective and lipid lowering effect | |||||
| Leaves obtained near to NBRI, Lucknow, India | Ethanolic extract | carbon tetrachloride induced Wistar rats | Significant hepatoprotective effect was reported at oral dose of 450 mg/kg. Effects were comparable to silymarin. | [75] | |
| ASLs extract | Ethanolic extract |
Diethylnitrosamine induced Swiss albino mice | Dose of 5 g/Kg exhibited hepatoprotective effects. | [76] | |
| ASLs extract | Aqueous extracts | Albino rats | ASLs extract protect the hepatic cells, paracetamol-induced increased level of bilirubin, cholesterol, and triglycerides level, which get normalised after treatment. | [77] | |
| ASLs extract | Methanolic extract | 5,7,40-trihydroxy- 6,30dimethoxy flavone 3-O-a-L-rhamnopyranoside | Wistar albino rats | Significantly reduced hepatic lipid peroxidation and improved serum lipid profile. | [78] |
| ASLs collected from Madurai, TN, India | Methanolic extract | - | Isoniazid-rifampicin induced rats | ALs extract protects against rifampicin-induced oxidative liver injury. | [79] |
| Leafy twigs of A. squamosa | Methanolic extract | - | Streptozotocin induced mice diabetic models | Significantly lower levels of TC and TGs was reported compared to diabetic control mice. | [74] |
| Fresh ASLs collected from Al-Nobaria, Egypt | Aqueous and ethanolic extract | - | Alloxan-induced hyperglycemic rats | Significantly reduced CL, TGs, and LDL-cholesterol and increased HDL-cholesterol compared to diabetic rats. | [80] |
| ASLs collected near Udaipur, India | 70% alcohol | - | Streptozotocin induced Albino rats | Maintained the lipid profile (reduced CL, TGs, and LDL-cholesterol and increased HDL). | [81] |
| ASLs were collected near IARI, New Delhi, India | Ethanolic extract | - | Alloxan and streptozotocin induced Wistar rats and albino rabbits | After 15 days of treatment, lipid profile maintains nearly normal level and increased the HDL cholesterol. | [69] |
| ASLs extract | Water extract | - | Streptozotocin induced Albino Wistar rats | Treatment enhanced the activity of antioxidant enzyme and reduces MDA, CL, and TGs. | [66] |
FBG—fasting blood glucose; BGL—blood glucose level; STZ—streptozotocin; TC—total cholesterol; TG—triglyceride; LDL—low density lipoprotein; HDL—high density lipoprotein; IR-β—insulin receptor-β; IRS-1—insulin receptor substrate-1; GLUT 4—glucose transporter type 4; PI3 kinase—phosphoinositide 3-kinase; PTP1B—protein-tyrosine phosphatase 1B; b.i.d.—twice a day; p.o.—by mouth.