Antihyperglycemic and antihyperlipidemic effects of fruit extract of Hodgsonia heteroclita (Roxb.) Hook. f. & Thomson in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice. MATERIALS AND METHODS: The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24'3.85″ N 90°16'22.30″ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita. RESULTS: It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents. CONCLUSION: The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes.

Elucidation of anti-hyperglycemic activity of Psidium guajava L. leaves extract on streptozotocin induced neonatal diabetic Long-Evans rats.

BACKGROUND: Psidium guajava L (Guava) belongs to the Myrtaceae family and has been claimed to possess several pharmacological properties including antidiabetic. OBJECTIVE: This study was designed to evaluate the anti-hyperglycemic activity of P guajava L leaves aqueous extract on neonatal streptozotocin-induced type 2 diabetic model rats. METHODS: Streptozotocin was induced (90 mg/kg) intraperitoneally to 48 h old Long Evans rat pups. After three months, 18 male type-2 diabetic model rats were confirmed by OGTT (FG > 7 mmol/L). Therefore, experimental rats were divided into three groups 2) Diabetic water control (10 ml/kg), 3) Gliclazide treated (20 mg/kg), and 4) Extract treated group (1.25g/kg)] Six normal female rats comprised group 1 [Non-diabetic water control (10 ml/kg)]. All rats were treated orally with their respective treatment for 28 consecutive days. Blood samples were collected on 0 days (by tail cut method) and the end day (by cardiac puncture) of the experiment. The anti-hyperglycemic activity was evaluated by measuring fasting glucose, serum insulin, lipid profile, hepatic glycogen content, and intestinal glucose absorption by standard methods. RESULTS: The serum glucose level of extract treated group was decreased by 16% as well as significantly (p<0.05) increased the serum insulin level (M±SD, 0 day vs 28thday; 0.319 ± 0.110 vs 0.600 ± 0.348, µg/L). Moreover, the extract-treated group also significantly (p<0.05) enhanced liver glycogen content and inhibited glucose absorption from the upper intestine. Besides, a significant (p < 0.05) reduction of LDL-cholesterol level was found in the extract-treated group (M±SD, 55 ± 33 vs 14 ± 9, mg/dl) compared with baseline values where other groups did not show any statistically remarkable changes. CONCLUSION: Current study concludes that P guajava leaves aqueous extract enhances insulin secretion from pancreatic beta-cells and promotes glycogen synthesis in the liver. The extract also inhibits glucose absorption from the upper intestine and improves dyslipidemia to some extent. Therefore, possesses the potential for drug development against T2DM.

Antihyperglycemic and anti-type 2 diabetic activity of marine hydroquinone isolated from brown algae (Dictyopteris polypodioides).

Background and aims: Brown algae (Dictyopteris polypodioides) extract (DP) presented high inhibitory potential against α-amylase. The present study aims to isolate, purify and evaluate the antihyperglycemic and anti-type 2 diabetic activities of marine hydroquinone from DP. Methods: Marine hydroquinones were isolated using silica gel, HPLC, and NMR spectroscopy was used to identify compound 1 and compound 2 as zonarol and isozonarol, respectively. The anti-hyperglycemic and anti-type 2 diabetic activities of zonarol were investigated by in vitro assay (α-amylase, α-glucosidase), Lineweaver-Burk plot and Type 2 diabetes mellitus model (T2DM) mice induced by streptozotocin (STZ). Result: Zonarol had the highest content and the strongest inhibitory activity against α-glucosidase (IC50 value of 6.03 mg L-1) and α-amylase (IC50 value of 19.29 mg L-1) in a competitive inhibition and mix-type manner, respectively. The maltose and starch loading tests revealed that zonarol significantly reduced postprandial glycemia after 30 min loading (9.12 and 8.12 mg/dL, respectively), compared to normal (11.37 and 12.37 mg/dL, respectively). Zonarol exhibited pancreatic islet cell rejuvenation, as evidenced by increased pancreatic islet mass, and hence helps in the restoration of insulin levels and therefore improves the glucose metabolism in STZ-induced diabetic mice. Zonarol treatment in T2DM elevated abundant levels of main SCFAs (propionate, butyrate, and valeric acid), which are closely related to glucose metabolism homeostasis. Conclusion: Our finding indicates that zonarol could be used as a food supplement to treat hyperglycemia and diabetes.

Structurally diverse polycyclic polyprenylated acylphloroglucinols with protective effect on human vein endothelial cells injured by high-glucose from Hypericum acmosepalum N. Robson.

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.

Anti-Hyperglycemic Effects of Refined Fractions from Cyclocarya paliurus Leaves on Streptozotocin-Induced Diabetic Mice.

To identify the chemical components responsible for the anti-hyperglycemic effect of Cyclocarya paliurus (Batal.) Iljinsk (Juglandaceae) leaves, an ethanol extract (CPE) and a water extract (CPW) of C. paliurus leaves, as well as their total flavonoids (CPF), triterpenoids (CPT) and crude polysaccharides (CPP), were prepared and assessed on streptozotocin (STZ)-induced diabetic mice. After being orally administrated once a day for 24 days, CPF (300 mg/kg), CPP (180 mg/kg), or CPF+CPP (300 mg/kg CPF + 180 mg/kg CPP) treatment reversed STZ-induced body weight and muscle mass losses. The glucose tolerance tests and insulin tolerance tests suggested that CPF, CPP, and CPF+CPP showed anti-hyperglycemic effect in STZ-induced diabetic mice. Furthermore, CPF enhances glucose-stimulated insulin secretion in MIN6 cells and insulin-stimulated glucose uptake in C2C12 myotubes. CPF and CPP suppressed inflammatory cytokine levels in STZ-induced diabetic mice. Additionally, CPF and CPP improved STZ-induced diabetic nephropathy assessed by H&E staining, blood urea nitrogen content, and urine creatinine level. The molecular networking and Emperor analysis results indicated that CPF showed potential anti-hyperglycemic effects, and HPLC-MS/MS analysis indicated that CPF contains 3 phenolic acids and 9 flavonoids. In contrast, CPT (650 mg/kg) and CPC (300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT) did not show anti-hyperglycemic effect. Taken together, polysaccharides and flavonoids are responsible for the anti-hyperglycemic effect of C. paliurus leaves, and the clinical application of C. paliurus need to be refined.

Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential.

Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.

Identification of baicalin from Bofutsushosan and Daisaikoto as a potent inducer of glucose uptake and modulator of insulin signaling-associated pathways.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM.

Flowers of Clerodendrum volubile modulates redox homeostasis and suppresses DNA fragmentation in Fe2+ - induced oxidative hepatic and pancreatic injuries; and inhibits carbohydrate catabolic enzymes linked to type 2 diabetes.

INTRODUCTION: Medicinal plants have long been recognized for their roles in the treatment and management of diabetes and its complications. The antioxidative and antidiabetic properties of Clerodendrum volubile flowers were investigated in vitro and ex vivo. METHODS: The flowers were sequentially extracted with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and water). The concentrated extracts were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols. Their inhibitory activities were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phosphatase activities. Their anti-oxidative and anti-apoptotic effects on Fe2+-induced oxidative injuries were also investigated in pancreatic and hepatic tissues ex vivo. RESULTS: The extracts showed potent free radical scavenging activity and significantly (p < 0.05) inhibited all studied enzymes. The GSH level was significantly (p < 0.05) elevated in both tissues with concomitant increase in superoxide dismutase (SOD) and catalase activities as well as reduced levels of malondialdehyde (MDA). The extracts significantly (p < 0.05) suppressed DNA fragmentation in hepatic tissue. These activities were dose-dependent. The ethanol extract showed the best activity and can be attributed to the synergetic effect of its chemical constituents identified via gas chromatography-mass spectroscopy (GC-MS). CONCLUSION: These results suggest the antioxidative, antidiabetic and anti-obesogenic potentials of C. volubile flowers.

Phenolic constituents and modulatory effects of Raffia palm leaf (Raphia hookeri) extract on carbohydrate hydrolyzing enzymes linked to type-2 diabetes.

This study sought to investigate the effects of Raffia palm (Raphia hookeri) leaf extract on enzymes linked to type-2 diabetes mellitus (T2DM) and pro-oxidant induced oxidative stress in rat pancreas. The extract was prepared and its α-amylase and α-glucosidase inhibitory effects were determined. Radical [2,2-diphenyl-1-picrylhydrazyl (DPPH)] scavenging and Fe2+-chelating abilities, and inhibition of Fe2+-induced lipid peroxidation in rat pancreas homogenate were assessed. Furthermore, total phenol and flavonoid contents, reducing property, and high performance liquid chromatography diode array detector (HPLC-DAD) fingerprint of the extract were also determined. Our results revealed that the extract inhibited α-amylase (IC50 = 110.4 µg/mL) and α-glucosidase (IC50 = 99.96 µg/mL) activities in concentration dependent manners which were lower to the effect of acarbose (amylase: IC50 = 18.30 µg/mL; glucosidase: IC50 = 20.31 µg/mL). The extract also scavenged DPPH radical, chelated Fe2+ and inhibited Fe2+-induced lipid peroxidation in rat pancreas all in concentration dependent manners with IC50 values of 402.9 µg/mL, 108.9 µg/mL and 367.0 µg/mL respectively. The total phenol and flavonoid contents were 39.73 mg GAE/g and 21.88 mg QAE/g respectively, while the reducing property was 25.62 mg AAE/g. The HPLC analysis revealed the presence of chlorogenic acid (4.17 mg/g) and rutin (5.11 mg/g) as the major phenolic compounds in the extract. Therefore, the ability of the extract to inhibit carbohydrate hydrolyzing enzymes and protect against pancreatic oxidative damage may be an important mechanisms supporting its antidiabetic properties and could make Raffia palm leaf useful in complementary/alternative therapy for management of T2DM. However, further studies such as in vivo should be carried out.

In vitro and in vivo reduction of post-prandial blood glucose levels by ethyl alcohol and water Zingiber mioga extracts through the inhibition of carbohydrate hydrolyzing enzymes.

BACKGROUND: Type 2 diabetes is a serious problem for developed and developing countries. Prevention of prediabetes progression to type 2 diabetes with the use of natural products appears to be a cost-effective solution. Zingiber mioga has been used as a traditional food in Asia. Recent research has reported the potential health benefits of Zingiber mioga, but the blood glucose reducing effect has not been yet evaluated. METHODS: In this study Zingiber mioga extracts (water and ethanol) were investigated for their anti-hyperglycemic and antioxidant potential using both in vitro and animal models. The in vitro study evaluated the total phenolic content, the oxygen radical absorbance capacity (ORAC) and the inhibitory effect against carbohydrate hydrolyzing enzymes (porcine pancreatic α-amylase and rat intestinal sucrase and maltase) of both Zingiber mioga extracts. Also, the extracts were evaluated for their in vivo post-prandial blood glucose reducing effect using SD rat and db/db mice models. RESULTS: Our findings suggest that the ethanol extract of Zingiber mioga (ZME) exhibited the higher sucrase and maltase inhibitory activity (IC50, 3.50 and 3.13 mg/mL) and moderate α-amylase inhibitory activity (IC50, >10 mg/mL). Additionally, ZME exhibited potent peroxyl radical scavenging linked antioxidant activity (0.53/TE 1 µM). The in vivo study using SD rat and db/db mice models also showed that ZME reduces postprandial increases of blood glucose level after an oral administration of sucrose by possibly acting as an intestinal α-glucosidase inhibitor (ZME 0.1 g/kg 55.61 ± 13.24 mg/dL) CONCLUSION: The results indicate that Zingiber mioga extracts exhibited significant in vitro α-glucosidase inhibition and antioxidant activity. Additionally, the tested extracts demonstrated in vivo anti-hyperglycemic effects using SD rat and db/db mice models. Our findings provide a strong rationale for the further evaluation of Zingiber mioga for the potential to contribute as a useful dietary strategy to manage postprandial hyperglycemia.

Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz.

In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats. The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed.