Antioxidants of commercial interest from Homalium tomentosum attenuates hepatocellular necrosis: Insights from experimental and computational studies.

Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl4)-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-ß; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC-MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski's rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-ß and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biobased materials for the pharmaceutical and food industries.

Hydrolea zeylanica improves cognitive impairment in high-fat diet fed-streptozotocin-induced diabetic encephalopathy in rats via regulating oxidative stress, neuroinflammation, and neurotransmission in brain.

Type2 diabetes mellitus is a progressive metabolic disorder characterized by ß-cell dysfunction with the increase in hepatic glucose synthesis and insulin resistance which leads to microvascular complications like diabetic encephalopathy that impairs cognitive dysfunctions, and dementia. The green and leafy vegetables of Hydrolea zeylanica are used in diet as rich source of nutrition, dietary fibers in reducing malnutrition and keeps in control the blood sugar level to treat diabetes related vascular complications. This study investigated the effect of hydroalcohol extracted fraction of leaves of H. zeylanica (HHZ) on high-fat diet fed-streptozotocin (HFD/STZ)-induced diabetes encephalopathy in experimental rats, and quantified the flavonoids, nutrients contents by HPLC analysis. HHZ demonstrated potential cellular antioxidant protection in ORAC, CAP-e tests. HHZ showed mixed competitive inhibition towards acetylcholinesterase (AChE), and butyrylcholineserase (BChE) activities, and exhibited dose dependent inhibition to both neurotransmitter activities. After 4 weeks administration of HHZ (oral, 300, and 400 mg/kg b.w.) in HFD/STZ-induced diabetic rats, HHZ-400 significantly (p < 0.001) improved the learning and memory impairment with the reduction in serum glucose and elevation in insulin level in encephalopathy rats. It also significantly (p < 0.001) improved oxidative (MDA, SOD, CAT, and GSH), and proinflammatory markers (TNF-α, IL-6, and hs-CRP) with the reduction in cholinesterase (AChE, BChE) and ß-secretase (BACE1, BACE2) activities as evidenced by histological architecture of cortex in diabetic encephalopathy rats. Diet rich source of flavonoids e.g., quercetin, caffeic acid, rutin, gallic acid, and ferulic acid, nutrients, and vitamins in H. zeylanica enhanced the cellular antioxidant protection by reducing oxidative stress, neuroinflammation and neurotransmission in the brain of diabetic encephalopathy 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.

Ameliorative effects of Hydrolea zeylanica in streptozotocin-induced oxidative stress and metabolic changes in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrolea zeylanica L. Vahl. (Hydroleaceae) is an aquatic medicinal plant used as leafy vegetable in some parts of India. In south Odisha and Hazaribag district of Jharkhand, India, decoction of leaves is used as household remedy for diabetes. To our knowledge, no prior studies have examined the antidiabetic activity of H. zeylanica to validate its ethnomedicinal claim. PURPOSE: With this aim in mind, we examined the bioactivity of hydroalcohol fraction of leaves of H. zeylanica (HAHZ) in streptozotocin-induced oxidative stress in diabetic rats. MATERIALS AND METHODS: In vitro antidiabetic and free radical scavenging activities of different fractions of H. zeylanica were performed. The most effective bioactive fraction e.g. HAHZ was considered for kinetic studies to understand the mode of inhibition of α-glucosidase and α-amylase. To understand the chemical composition, GC-MS/MS and LC-MS/MS analysis of HAHZ were performed. To find out the molecular mechanism of action of HAHZ, streptozotocin-induced oxidative stress and metabolic changes in diabetic rats were studied. RESULTS: HAHZ demonstrated significantly higher radical scavenging and antidiabetic activities. Kinetic analysis revealed that HAHZ inhibited α-glucosidase competitively, and α-amylase mixed competitively. To understand the chemical composition, GC-MS/MS and LC-MS/MS analysis of HAHZ identified 32 compounds and among which R-limonene (0.52%), perillartine (0.41%), N-formyl-L-lysine (1.49%), limonen-6-ol, pivalate (1.43%), lidocaine (1.70%) and gamolenic acid (2.80%) were reported to have antioxidant and antidiabetic activities. HAHZ-400 mg/kg showed significant (p < 0.001) improvement in serum markers (SGOT, SGPT, ALP, total bilirubin, total protein, triglycerides, total cholesterol, HDL-C, LDL-C) and oxidative markers (MDA, SOD, CAT, GSH) in serum, liver and pancreas at effective dose dependent manner. In histopathological observation, HAHZ-400 mg/kg showed marked improvement in restoring cellular architecture of liver and pancreas. CONCLUSION: In diabetic rats, the improvement in glycemic control mechanism was achieved upon stimulating insulin secretion by R-limonene, perillartine, N-formyl-L-lysine, limonen-6-ol, pivalate, lidocaine and gamolenic acid of HAHZ.