Homalium zeylanicum attenuates streptozotocin-induced hyperglycemia and cellular stress in experimental rats via attenuation of oxidative stress imparts inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Homalium zeylanicum (Gardner) Benth (Salicaceae) leaves are being used as folklore medicine to treat diabetes by the local folk of Andhra Pradesh, India. The medicinal claim of this plant with hypoglycaemic effects was initially studied by the authors. Results demonstrated the important antioxidant activities of the hydroalcohol fraction of leaves of H. zeylanicum leaves (HAHZL) were positively correlated with phenols and flavonoids contents. AIM OF THE STUDY: Based on the previous findings, additional research is needed to examine the efficacy of using HAHZL to treat hyperglycemia. We therefore investigated in vitro and in vivo glycemic response of HAHZL, and evaluation of possible mechanism of bioactive molecules in mitigating streptozotocin-induced cellular stress in experimental rats via attenuation of oxidative stress imparts inflammation. METHODS: GC-MS/MS analysis of HAHZL was carried out to identify bioactive constituents. In vitro antidiabetic (α-glucosidase, α-amylase) and anti-inflammatory activities were investigated. HFD/low-STZ-prompted diabetic Wistar rats were administered with HAHZL (300 and 400 mg/kg; oral) for 28 days. Blood serum, oxidative stress, inflammation, DNA damage, and antidiabetic markers of pancreas and liver were determined. Histopathological studies of liver and pancreas were performed to assess the protective role of HAHZL. RESULTS: GC-MS/MS study revealed 7 bioactive compounds e.g., Phenol, 4-ethenyl-, acetate (28.68%), hydroquinone (9.10%), n-hexadecanoic acid (0.55%), phytol (0.57%), arbutin (17.65%), Vitamin E (1.04%), ß-Sitosterol (1.54%) which possess antioxidant, anti-inflammatory and anti-diabetic activities. HAHZL showed significant in vitro glycemic response as evidenced by the inhibition of α-amylase, and α-glucosidase activities. Lineweaver-Burk plot revealed that HAHZL exhibited competitive and mixed competitive inhibition towards α-amylase and α-glucosidase, respectively. HAHZL at 400 mg/kg modulated the pathophysiology associated with HFD/STZ-induced type2 diabetes mellitus and significantly (p < 0.001) improved antihyperglycemic (SG, SI, HOMA-IR, and HbA1C), antidyslipidemic (TC, HDL-C, LDL-C, and TG), antioxidative (MDA, SOD, CAT, GSH, and 8-OHdG) and anti-inflammatory (TNF-α, and CRP) markers in serum, pancreas and liver. In vitro and in vivo test results were corroborated by the improvement of pancreatic and hepatic tissue architecture in diabetic rats. CONCLUSION: HAHZL bearing bioactive components phenol, 4-ethenyl-,acetate, hydroquinone, n-hexadecanoic acid, arbutin, phytol, vitamin E and ß-sitosterol balanced glycemic level by normalising the levels of glycaemic indices, lipid profile, pancreas and liver functional markers in STZ-induced T2DM rats.

The modulatory role of prime identified compounds in the bioactive fraction of Homalium zeylanicum in high-fat diet fed-streptozotocin-induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Homalium zeylanicum (Gardner) Benth. is a medicinal plant traditionally used in controlling diabetes which thus far has been assessed by the authors only to a very limited extent. PURPOSE: To fill the research gap in the literature review, we investigated the antihyperglycemic effects of hydro alcohol fraction of bark of H. zeylanicum (HAHZB) by modulating oxidative stress and inflammation in high-fat diet fed-streptozotocin (HFD/STZ)-induced type-2 diabetic rats. MATERIALS AND METHODS: To understand the antioxidant capacity of HAHZB, oxygen radical absorbance capacity (ORAC) and cell-based antioxidant protection in erythrocytes (CAP-e) were performed. GC-MS/MS analysis was performed to assess the bioactive components in HAHZB. HFD/STZ-induced diabetic rats were treated orally with HAHZB (300 and 400 mg/kg) for 28 days. After the end of the experiment, marker profiling and histopathological observation of blood and pancreas were examined. The study also highlights interaction between diabetes, oxidative stress and inflammation by examining the increased pro-inflammatory cytokines e.g. TNF-α and C-reactive protein (CRP) promotes DNA damage e.g. oxidation of 8-hydroxy-2-deoxyguanosine (8-OHdG) in chronic hyperglycaemia. RESULTS: In ex vivo cellular antioxidant capacity of -CAP-e and ORAC assays, HAHZB showed remarkable free radical scavenging ability in a dose dependent manner. GC-MS/MS analysis identified 28 no. of compounds and out of which, oleic acid (1.03%), ethyl tridecanoate (11.77%), phytol (1.29), 9,12-octadecadienoic acid, methyl ester, (E,E)-(5.97%), stigmasterol (1.30%) and ß-sitosterol (2.86%) have antioxidant, anti-inflammatory and anti-diabetic activities. HAHZB 400 mg/kg significantly (p < 0.001) improved the lipid profile (TC: 74.66 ± 0.59, HDL-C: 22.08 ± 0.46, LDL-C: 38.06 ± 0.69, and TG: 171.92 ± 1.01 mg/dL) as well as restoring antidiabetic markers (SG: 209.62 ± 1.05 mg/dL, SI: 15.07 ± 0.11 µIU/mL, HOMA-IR: 7.79 ± 0.04 %, and HbA1C: 8.93 ± 0.03 %) and renal functional markers (Tg: 291.26 ± 0.57 pg/mL, BUN: 23.79 ± 0.14 mg/dL, and Cr: 1.34 ± 0.04 mg/dL) in diabetic rats. Oxidative stress markers of pancreas (MDA: 3.65 ± 0.17 nM TBARS /mg protein, SOD: 3.14 ± 0.28 U/mg protein, CAT: 7.88 ± 0.23 U/mg protein, GSH: 12.63 ± 0.28 µM/g of tissue) were restored to normal as evidenced by histological architecture of pancreatic islet cells. The increased level of pro-inflammatory cytokines and oxidative DNA damage were significantly restored (TNF-α: 54.48 ± 3.19 pg/mL, CRP: 440.22 ± 7.86 ng/mL, and 8-OHdG: 63.65 ± 1.84 ng/mL) by HAHZB in diabetic rats. CONCLUSION: The present findings confirm that the presence of bioactive compounds in HAHZB exert therapeutic protective effect by decreasing oxidative, inflammation and pancreatic ß-cell damage in oxidative stress induced diabetic rats.

Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells.

Cervical cancer and precancerous lesions of the cervix continue to be a global health issue, and the medication for the treatment for chronic HPV infection so far has not been effective. Potential anticancer and anti HPV activities of two known phytochemicals, Curcumin and Ellagic acid were evaluated in HeLa cervical cancer cells. Curcumin is a natural compound found in the root of Curcuma longa plant and Ellagic acid a polyphenol found in fruits of strawberries, raspberries and walnuts. The combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay. Besides this, Curcumin and Ellagic acid also restore p53, induce ROS formation and DNA damage. Mechanistic study further indicated that Curcumin and Ellagic acid show anti-HPV activity as evidenced by decrease in the HPV E6 oncoprotein on HeLa cells.