Phytochemical profiling, anti-hyperglycemic, antifungal, and radicals scavenging potential of crude extracts of Athyrium asplenioides- an in-vitro approach.

This research was aimed to evaluate the phytochemical profile, antifungal, anti-hyperglycemic, as well as antioxidant activity competence of different extracts of Athyrium asplenioides through in-vitro approach. The A. asplenioides crude methanol extract contained considerable quantity of pharmaceutically precious phytochemicals (saponins, tannins, quinones, flavonoid, phenols, steroid, and terpenoids) than others (acetone, ethyl acetate, and chloroform). Interestingly, the crude methanol extract showed remarkable antifungal activity against Candida species (C. krusei: 19.3 ± 2 mm > C. tropicalis: 18.4 ± 1 mm > C. albicans: 16.5 ± 1 mm > C. parapsilosis: 15.5 ± 2 mm > C. glabrate: 13.5 ± 2 mm > C. auris: 7.6 ± 1 mm) at a concentration of 20 mg mL-1. The crude methanol extract also showed remarkable anti-hyperglycemic activity on concentration basis. Surprisingly, remarkable free radicals scavenging potential against DPPH (76.38%) and ABTS (76.28%) free radicals at a concentration of 20 mg mL-1. According to the findings, the A. asplenioides crude methanol extract contains pharmaceutically valuable phytochemicals and may be useful for drug discovery.

Evaluation of anti-inflammatory, diuretic and oral glucose tolerance activities of phenolic compound-rich fractions of Hammada articulata in Albino Wistar rats.

Hammada articulata is a plant widely used by the locals of the Algerian Sahara for multiple medicinal purposes. However, little was known about its chemical composition and the mechanisms of its bioactivity. For this purpose, the derived extracts [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 80% ethanol extract of its aerial parts, were evaluated for their anti-inflammatory, diuretic, and anti-hyperglycemic activities in vivo. A preliminary phytochemical screening of H. articulata extracts showed the presence of a variety of secondary metabolites. RP-HPLC/DAD was used to analyze some fractions obtained by fractionation of the three derived extracts, by column chromatography and chosen because of the abundance and simplicity of their chemical composition. The fractions obtained from EtOAc and n-BuOH extracts showed a particular richness in phenolic compounds mainly naringenin, quercetin, kaempferol, myricetin, and rutin, which were known for their many interesting biological activities. The three derived extracts from H. articulata were assessed for their anti-inflammatory activity in the carrageenan-induced edema model in rats and their diuretic activity using hydrochlorothiazide (HCTZ) as a diuretic reference. All extracts showed considerable anti-inflammatory activity; the highest was registered in the group treated with the n-BuOH extract. However, for the diuretic activity, only the chloroform extract was active, with a diuretic spectrum similar to that of the standard diuretic HCTZ. The anti-hyperglycemic effect was carried out on the three derived extracts administered orally at a dose of 200 mg/kg, using the glucose tolerance test after gavage with the extracts. The EtOAc and n-BuOH extracts showed significant anti-hyperglycemic activity, improving oral glucose tolerance in normal rats.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

Anti-hyperglycemic activity of aqueous extracts of cells produced in Ibervillea sonorae (S. Watson) Green cell culture on murine model / Actividad anti-hiperglucémica del extracto acuoso de células producidas en cultivo celular de Ibervillea sonorae (S. Watson) Green en un modelo murino

Ibervillea sonorae (S. Watson) Greene, is a plant native to Mexico, where its roots have been used traditionally for treating Diabetes Mellitus. The aim of this work was to establishment of cell cultures of stem explants of I. sonorae and evaluation of the anti-hyperglycemic activity of cell aqueous extract on a murine model of streptozotocin-induced diabetic rats. Cell extracts had 2.29 mg palmitic acid/g extracted, and other compounds with pharmacological activities like palmitoyl ethanolamide and palmitoyl tryptamine were also identified. Diabetic rats treated with aqueous cell extract decreased glucose levels from 350 mg/dL to 145 mg/dL, AST and ALT from 164 U/L to 49 U/L and 99 U/L to 53 U/L, respectively. Additionally, there were no changes in the cellular morphology of the pancreas, liver, kidneys, and spleen. These results revealed that the cell aqueous extract from stem explants has anti-hyperglycemic activity.

Ibervillea sonorae (S. Watson) Greene, es una planta originaria de México, donde sus raíces se han utilizado tradicionalmente para el tratamiento de la Diabetes Mellitus. El objetivo de este trabajo fue el establecimiento de cultivos celulares de explantes de tallo de I. sonorae y la evaluación de la actividad anti-hiperglucémica del extracto acuoso celular en un modelo de ratas diabéticas inducidas con estreptozotocina. El extracto celular contiene 2.29 mg de ácido palmítico/g extracto y se identificaron otros compuestos como palmitoil etanolamida y palmitoil triptamina. Las ratas diabéticas tratadas con extracto celular disminuyeron los niveles de glucosa de 350 mg/dL a 145 mg/dL, AST y ALT de 164 U/L a 49 U/L y 99 U/L a 53 U/L, respectivamente. Además, no hubo cambios en la morfología celular del páncreas, hígado, riñones y bazo. Estos resultados indican que el extracto de células de explantes de tallo de I. sonorae tiene actividad anti-hiperglucémica.

Anti-hyperglycemic fraction from Alternanthera sessilis L. leaves gets elucidated following bioassay-guided isolation and mass spectrometry

Abstract The anecdotal use of Alternanthera sessilis L. as a relief for diabetes has been known in the Philippines for generations, and antidiabetic activity of similar varieties in other countries is likewise documented. However, the compounds responsible for this activity remain unclear. This study aims to isolate the anti-hyperglycemic fraction of local A. sessilis leaves and identify the compounds in this fraction. Methanol extract of A. sessilis leaves and its hexane, ethyl acetate (ASE), and water fractions were administered to alloxan-induced diabetic mice. ASE (250mg/kg) had the highest anti-hyperglycemic activity at 6-h post-treatment (25.81%±12.72%), with almost similar blood glucose reduction rate as metformin (30.13±3.75%, p=0.767). Repeated fractionation employing chromatographic separation techniques followed by in vivo anti-hyperglycemic assay yielded partially purified subfractions. A. sessilis ethyl acetate subfraction 4-2 (100mg/kg) displayed remarkable suppression of blood glucose rise in diabetic mice at 6-h post-treatment (26.45±3.75%, p<0.0001), with comparable activity with metformin (100mg/kg, 27.87±5.65%, p=0.652). Liquid chromatography/mass spectrometry showed eight distinct peaks, with four peaks annotated via the Traditional Chinese Medicine library and custom library for A. sessilis. Among these, luteolin, apigenin, ononin, and sophorabioside were identified as putative compounds responsible for the anti-hyperglycemic activity. This result provided basis for the reported anecdotal claims and potential utility of the local variety of A. sessilis leaves as sources of anti-hyperglycemic agents

Antioxidant Activity and Inhibition of Carbohydrate Digestive Enzymes Activities of Artemisia campestris L.

BACKGROUND: Carbohydrate digestive enzymes play a major role in the management of the postprandial hyperglycemia. A chronic hyperglycemia can lead to serious health problems due to excessive production of several reactive oxygen species. Therefore, the inhibition of carbohydrate digestive enzyme and the use of antioxidant natural product can be an important strategy to control the glycaemia level and prevent against the complication of diabetes. AIM: The study aims to perform a phytochemical analysis, antioxidant activity, inhibitory effect on α -amylase, α -glucosidase (in vitro and in vivo) and the intestinal glucose absorption in Wistar rats of Artemisia campestris aqueous extract (AcAE) and hydro-ethanolic extract (AcEE). RESULTS: The test of total phenolic content, show that the AcAE has the highest quantity of polyphenol (44.65 ± 0.54 µ g GAE/mg extract) compared to the AcEE (31.7 ± 0.53 µ g GAE/mg extract) significantly. The amount of flavonoid and condensed tannins content in AcAE is 24.41 ± 3.57 µ g QrE/mg extract, 14.31 ± 5.26 µ g CE/mg respectively. The AcAE has also exhibit a great antioxidant activity in DPPH-scavenging and Ferric reducing antioxidant power assay (FRAP) compared to AcEE with an IC 50 = 0.355 ± 0.057 mg/mL and IC 50 = 0.269 ± 0.025 mg/mL. However, in a ß -carotene bleaching assay the AcEE has the highest effect with an IC 50 = 0.319 ± 0.097 mg/mL. The both extract of Artemisia campestris L. (250 mg/kg) decreased postprandial hyperglycemia in the normal and alloxane diabetic rats in a very significant manner after starch or sucrose administration as an α -amylase and α -glucosidase substrate respectively. This result is confirmed in vitro by a remarkable inhibitory effect on α -amylase digestive enzymes by an IC 50 = 1.259 ± 0.128 mg/mL and IC 50 = 0.602 ± 0.072 mg/mL receptively for AcAE and AcEE. For the α -glucosidase enzyme, the both extracts significantly inhibit α -glucosidase activity compared to the control and they are almost similar to each other. Using a jejunum perfusion technique (in situ), Artemisia campestris L. decrease the intestinal D-glucose absorption activity significantly compared to the control and comparable to the Phlorizin used as a positive control by an amount of glucose absorbed equal a 6.53 ± 0.57, 5.34 ± 0.64 and 4.71 ± 0.24 mg/10 cm/h, for AcAE, AcEE and Phlorizin respectively. CONCLUSIONS: These results showed that the Artemisia campestris L. has highest phenolic content, antioxidant activity and demonstrated a postprandial anti-hyperglycemic effect via the inhibiting of the carbohydrate digestive enzyme ( α -amylase and α -glucosidase) and the intestinal glucose absorption.

Gut microbiota modulation by plant polyphenols in koi carp (Cyprinus carpio L.).

Plant polyphenol supplementation may improve fish health in aquaculture systems. To assess the potential benefits and function mechanism of plant polyphenols in aquaculture, fish were fed either basal feed (CON) or the basal feed supplemented with 500 mg/kg of curcumin (CUR), oligomeric proanthocyanidins (OPC), chlorogenic acid (CGA), or resveratrol (RES). After an 8-week feeding experiment, blood samples were used to analyze the concentrations of biochemical indices. Gut samples were collected to evaluate microbiota, short chain fatty acid (SCFA) levels, and gene expression. The results indicated that polyphenol administration reduced serum glucose and insulin. Lysozyme activity was enhanced by OPC and CGA, and superoxide dismutase activity was increased by CUR, OPC, and CGA. The gut microbial structure of the RES group was segregated from that of the CON, and the genus Bacteroides was identified as a potential biomarker in the CUR, CGA, and RES groups. Total gut SCFA increased in the CUR, CGA, and RES groups. A strong correlation was observed between Bacteroides and SCFA. In conclusion, dietary polyphenols have distinct anti-inflammatory, anti-oxidant, and anti-hyperglycemic activities that may be closely associated with their microbiota-modulation effects.

Evaluation of Possible Antioxidant, Anti-Hyperglycaemic, Anti-Alzheimer and Anti-Inflammatory Effects of Teucrium polium Aerial Parts (Lamiaceae).

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 µg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 µg/mL and mild activity in the ß-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 µg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 µg GAE/mg) and flavonoids (24.30 ± 0.44 µg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research.

A Glimpse of Inflammation and Anti-Inflammation Therapy in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and a major cause of end-stage kidney disease (ESKD). The pathogenesis of DKD is very complex and not completely understood. Recently, accumulated evidence from in vitro and in vivo studies has demonstrated that inflammation plays an important role in the pathogenesis and the development of DKD. It has been well known that a variety of pro-inflammatory cytokines and related signaling pathways are involved in the procession of DKD. Additionally, some anti-hyperglycemic agents and mineralocorticoid receptor antagonists (MRAs) that are effective in alleviating the progression of DKD have anti-inflammatory properties, which might have beneficial effects on delaying the progression of DKD. However, there is currently a lack of systematic overviews. In this review, we focus on the novel pro-inflammatory signaling pathways in the development of DKD, including the nuclear factor kappa B (NF-κB) signaling pathway, toll-like receptors (TLRs) and myeloid differentiation primary response 88 (TLRs/MyD88) signaling pathway, adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathways, inflammasome activation, mitochondrial DNA (mtDNA) release as well as hypoxia-inducible factor-1(HIF-1) signaling pathway. We also discuss the related anti-inflammation mechanisms of metformin, finerenone, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonist and traditional Chinese medicines (TCM).

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function.

Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Bacteria translocation and systemic inflammatory response caused by intestinal barrier injury play a significant role in sepsis occurrence and deterioration, while hyperglycemia is linked to adverse outcomes in sepsis. Previous studies have shown that hyperglycemia is an independent risk factor for intestinal barrier injury. Concurrently, increasing evidence has indicated that some anti-hyperglycemic agents not only improve intestinal barrier function but are also beneficial in managing sepsis-induced organ dysfunction. Therefore, we assume that these agents can block or reduce the severity of sepsis by improving intestinal barrier function. Accordingly, we explicated the connection between sepsis, intestinal barrier, and hyperglycemia, overviewed the evidence on improving intestinal barrier function and alleviating sepsis-induced organ dysfunction by anti-hyperglycemic agents (eg, metformin, peroxisome proliferators activated receptor-γ agonists, berberine, and curcumin), and summarized some common characteristics of these agents to provide a new perspective in the adjuvant treatment of sepsis.

Machine Learning and In Vitro Chemical Screening of Potential α-Amylase and α-Glucosidase Inhibitors from Thai Indigenous Plants.

Diabetes mellitus is a major predisposing factor for cardiovascular disease and mortality. α-Amylase and α-glucosidase enzymes are the rate-limiting steps for carbohydrate digestion. The inhibition of these two enzymes is clinically used for the treatment of diabetes mellitus. Here, in vitro study and machine learning models were employed for the chemical screening of inhibiting the activity of 31 plant samples on α-amylase and α-glucosidase enzymes. The results showed that the ethanolic twig extract of Pinus kesiya had the highest inhibitory activity against the α-amylase enzyme. The respective ethanolic extract of Croton oblongifolius stem, Parinari anamense twig, and Polyalthia evecta leaf showed high inhibitory activity against the α-glucosidase enzyme. The classification analysis revealed that the α-glucosidase inhibitory activity of Thai indigenous plants was more predictive based on phytochemical constituents, compared with the α-amylase inhibitory activity (1.00 versus 0.97 accuracy score). The correlation loading plot revealed that flavonoids and alkaloids contributed to the α-amylase inhibitory activity, while flavonoids, tannins, and reducing sugars contributed to the α-glucosidase inhibitory activity. In conclusion, the ethanolic extracts of P. kesiya, C. oblongifolius, P. anamense, and P. evecta have the potential for further chemical characterization and the development of anti-diabetic recipes.

Cyclocarya paliurus (Batalin) Iljinskaja: Botany, Ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) also known as Sweet tea tree, Money tree, Money willow, green money plum, mountain willow and shanhua tree, is a native rare monocotyledonous plant in Southern China. It possesses numerous traditional benefits, including clearing heat, detoxification, producing saliva, slake thirst, anti-inflammatory, insecticidal, dispelling wind and relieving itching. It is also effective in preventing and treating diabetes, hypertension, hyperlipidemia, dizziness and swelling and pain, as well as reducing cholesterol, and modulating the functions of the immune system. The stem, leaves and bark of this plant are all medicinal parts, but the leaves have the highest research value. AIM OF THE STUDY: This article summarized the plant's botanical description, distribution, ethnopharmacology, phytochemical profiles and pharmacological for the first time, to provide possible directions for future development and research in brief. MATERIAL AND METHODS: The literature for this current manuscript was obtained from reports published from 1992 to May 2021 in diverse databases such as the China Knowledge Resource Integrated databases (CNKI), SciFinder, Google Scholar, Baidu Scholar, Elsevier and Pub-Med. The domestic and foreign references published about C. paliurus over recent years were collected, analyzed and summarized. RESULTS: The botanical characteristics of the fruits of C. paliurus are unique in having a central nutlet surrounded by a circular wing to distinguish the living genera of Juglandaceae. In traditional medicine, C. paliurus leaves are used by the local people of Southern China to make tea to prevent diabetes. More than 210 compounds have been isolated from C. paliurus. Among them, the characteristic 3,4-seco-dammaranes accounted for the most. Other compounds include dammarane tetracyclic triterpenoids, various pentacyclic triterpenoids, flavonoids, isosclerones, phenolic derivatives and polysaccharides. The plant extracts and compounds have been reported to exert various pharmacological activities, such as anti-hyperglycemic, anti-hyperlipidemic, anti-cancer, cytotoxic, anti-oxidative, anti-inflammatory, hepatoprotective, and anti-microbial activities. CONCLUSIONS: Comprehensive literature analysis shows that C. paliurus extract and its compounds have a variety of biological activities for the treatment of various diseases. The current modern pharmacology research is mostly related to the records of ethnic pharmacology, mainly in vitro research, relatively few in vivo research. Therefore, future studies should focus on this aspect. In addition, we also would like to recommend further research should concentrate on toxicity studies and quality control of C. paliurus to fill the study gap, as well as to provide theoretical support for the further development of the potential functions and clinical applications of the plant.

Ethnobotanical, phytochemical, toxicology and anti-diabetic potential of Senna occidentalis (L.) link; A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Senna occidentalis (L.) Link is a plant that has been used in medicine in some African countries, Asia and America. It is mainly used in Ayurvedic medicine in India. Several parts of this plant are used for preventing or treating diabetes, haematuria, rheumatism, typhoid, asthma, hepatotoxicity, disorders of haemoglobin and leprosy. AIM OF THE STUDY: This review outlines the pharmacological evidence supporting the potential of S. occidentalis to control or compensate for diabetes and associated complications, with intentions to sensitize the scientific community for future research on this promising plant. MATERIALS AND METHODS: Information on the anti-diabetic pharmacological studies of Senna occidentalis was collected from various scientific databases including Scopus, PubMed, ScienceDirect and Google Scholar. The studies were analyzed for the toxicological, phytochemical, anti-diabetic, hypoglycemic, anti-hyperlipidemia and antioxidative aspects of the different parts of S. occidentalis. RESULTS: Numerous phytochemical constituents (flavonoids, saponins, alkaloids, tannins, terpenes and glycosides) are present in this plant and are responsible for their anti-diabetic, hypoglycemic, anti-hyperlipidemic and antioxidative effects. The different plant parts appears to exert anti-diabetic effects by direct regulation of blood glucose, modulation of lipid profile and improving of antioxidant status and islet function. CONCLUSION: Senna occidentalis is rich in phytochemicals. The crude extracts of the different parts have valuable bioactive properties with potential ethnopharmacological relevance for diabetes management and treatment. Further bioassay guided phytochemical analyses of this plant are recommended to explore its therapeutic bioactive principles.

New Insights of Anti-Hyperglycemic Agents and Traditional Chinese Medicine on Gut Microbiota in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic disease characterized by chronic hyperglycemia. Human microbiota, which is regarded as a "hidden organ", plays an important role in the initiation and development of T2DM. In addition, anti-hyperglycemic agents and traditional Chinese medicine may affect the composition of gut microbiota and consequently improve glucose metabolism. However, the relationship between gut microbiota, T2DM and anti-hyperglycemic agents or traditional Chinese medicine is poorly understood. In this review, we summarized pre-clinical and clinical studies to elucidate the possible underlying mechanism. Some anti-hyperglycemic agents and traditional Chinese medicine may partly exert hypoglycemic effects by altering the gut microbiota composition in ways that reduce metabolic endotoxemia, maintain the integrity of intestinal mucosal barrier, promote the production of short-chain fatty acids (SCFAs), decrease trimethylamine-N-oxide (TMAO) and regulate bile acid metabolism. In conclusion, gut microbiota may provide some new therapeutic targets for treatment of patients with diabetes mellitus.

In-Vitro α-amylase, α-glucosidase Inhibitory Activities and In-Vivo Anti-Hyperglycemic Potential of Different Dosage Forms of Guduchi (Tinospora Cordifolia [Willd.] Miers) Prepared With Ayurvedic Bhavana Process.

Guduchi (Tinospora cordifolia [Willd.] Miers) is a flagship rejuvenating herb of Ayurveda with reported anti-diabetic potential. In the present study, different dosage forms of Guduchi stem (growing on neem tree) were developed by adopting Ayurvedic pharmaceutical process of Bhavana (levigation). Guduchi Churna (GC) was subjected to 07 times Bhavana separately with its own extracted juice, decoction and potable water, and dosage forms namely Svarasa Bhavita Guduchi Churna (SBGC), Kwatha Bhavita Guduchi Churna (KBGC), and Jala Bhavita Guduchi Churna (JBGC) were prepared. The present study was aimed to evaluate the role of Bhavana on the potentiation of therapeutic properties of Guduchi. Sequential solvent extracts (5, 10, 15 and 25%) of GC, SBGC, KBGC and JBGC were prepared in different solvents [phosphate buffer, hexane, dichloromethane (DCM), chloroform] and screened for the α-amylase and α-glucosidase inhibitory activity. The results revealed that phosphate buffer and DCM extracts of SBGC exhibited strong α-amylase inhibitory potential (>80% inhibition at 25% concentration) followed by KBGC, JBGC and GC with reference to the standard acarbose. In α-glucosidase inhibitory activity, maximum inhibition was observed in DCM and chloroform extracts of SBGC (>85% inhibition at 25% concentration), followed by KBGC (>80% inhibition at 25% concentration), JBGC and GC. In vivo anti-hyperglycemic studies were carried out by oral glucose tolerance test in Swiss albino mice. Test drugs (JBGC, KBGC, SBGC) treated groups showed marginal decrease of blood glucose levels in normo glycemic mice. However, the blood glucose level in test drug JBGC, KBGC and SBGC treated groups was still within normal range in overnight fasted mice. In oral glucose tolerance test, among all dosage forms SBGC (51.08%) produced pronounced anti-hyperglycemic effect followed by KBGC (42.57%) at a dose of 520 mg/kg. The GC, JBGC, KBGC and SBGC samples were also standardized using berberine (a well established anti-diabetic compound) as a marker compound by HPTLC fingerprint analysis. Findings of the present study indicate that SBGC and KBGC can be used in the treatment of diabetes mellitus and gives supporting evidence to Ayurvedic claims that the Bhavana process has pharmaceutico-therapeutic significance in Ayurvedic drug development.

Comprehensive chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba.

Extensive pharmacological research has demonstrated that Clerodendranthi Spicati Herba has an obvious anti-hyperglycemic effect via α-glucosidase inhibitory activity. However, the anti-hyperglycemic active fraction and its metabolic behavior in vivo have not been elaborated clearly. In this study, ultra-high-performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry with data filtering strategy, including mass defect screening, diagnostic product ions and neutral loss identification, was established for chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba. A total of 28 methoxylated flavonoids and 61 diterpenoids were rapidly identified. Four main known methoxylated flavonoids were purified and unambiguously identified by nuclear magnetic resonance analysis. Thirty-one absorbed diterpenoids, 12 absorbed methoxylated flavonoids, and 56 methoxylated flavonoids metabolites were identified in rat plasma, urine, bile, and feces after oral administration of anti-hyperglycemic active fraction. The methoxylated flavonoids were predominantly metabolized by demethylation, sulfation, and glucuronidation. Glucuronidation metabolites found in bile and urine after demethylation were dominant metabolites. Diterpenoids were absorbed into the blood mainly in the form of prototypes and excreted through bile and urine. These results indicated that methoxylated flavonoids and diterpenoids were responsible for α-glucosidase inhibitory activity, which might provide novel drug candidates for the management of diabetes mellitus.

Efficacy and Safety of a Traditional Herbal Combination in Patients with Type II Diabetes Mellitus: A Randomized Controlled Trial.

BACKGROUND: Capparis spinosa, Rosa canina, Securidaca securigera, Silybum marianum, Urtica dioica, Trigonella foenum-graecum and Vaccinium arctostaphylos are used traditionally as an herbal combination for treatment of diabetic patients in Iran. Despite the clinical evidence supporting their use in solitary form, no controlled human study has determined the efficacy and safety of their combination in treatment of diabetic patients. METHODS: A total 150 type II diabetic patients of both sexes under the oral anti-hyperglycemic drugs treatment (maximum 10 mg glyburide and 1000 mg metformin daily) were randomly assigned to three groups. The patients in each group received either herbal combination or placebo or metformin capsule daily for three months, without any change in their previous oral anti-hyperglycemic drugs dosage. Herbal combination, placebo and metformin capsules matched by shape and color were prepared in the Institute of Medicinal Plants Karaj, Iran. To assess the efficacy and safety of the treatments, the patients fasting plasma glucose, HbA1c, lipid profile, liver enzymes and renal function were determined at the beginning of the study and after three months. RESULTS: Results showed that after three months, the fasting plasma glucose, HbA1c and cholesterol levels in herbal combination were decreased significantly as compared to placebo group (20% and 12% respectively) and also compared to base line (25% and 15% respectively). The herbal combination was as effective as metformin in reduction of FPG (p = 0.001, p = 0.001) and HbA1c (p = 0.028 and p = 0.050 respectively) compared to placebo. No notable hepatic, renal and gastrointestinal side effects were observed in the trial groups. CONCLUSION: The results suggest that traditional herbal combination may safely improve glycemic control in type II diabetic patients with no significant adverse effect. [Formula: see text].

Role of nutraceutical starch and proanthocyanidins of pigmented rice in regulating hyperglycemia: Enzyme inhibition, enhanced glucose uptake and hepatic glucose homeostasis using in vitro model.

Dysregulation of glucose homeostasis result in hyperglycemia and pigmented rice, unique combination of high quality starch and phenolics has the potential in regulating it. In this study, pigmented rice was characterized in terms of nutraceutical starch (NS) and phenolic content. Further the effect of rice phenolics on carbolytic enzyme inhibition, glucose uptake, hepatic glucose homeostasis and anti-glycation ability was analyzed in vitro. The most relevant effect on enzyme inhibition (α-amylase: IC50-42.34 µg/mL; α-glucosidase: IC50:63.89 µg/mL), basal uptake of glucose (>39.5%) and anti-glycation ability (92%) was found in red rice (RR), than black rice (BR). The role of RR phenolics in regulating glucose homeostasis was deciphered using hepatic cell line system, which found up-regulation of glucose transporter 2 (GLUT2) and glycogen synthase 2 (GYS2); while expression of gluconeogenic genes were found down regulated. To our knowledge this study is the first report validating the role of starch-phenolic quality towards anti-hyperglycemic effect of RR.

Chemical characterization, antioxidant capacity, and anti-hyperglycemic effect of Stenocereus stellatus fruits from the arid Mixteca Baja region of Mexico.

The tunillo (Stenocereus stellatus [Pfeiffer] Riccobono) is a relatively little known cactus fruit with a significant pharmacological potential. However, all currently known variants are identified visually mostly on the basis of pulp color. Differences in chemical composition and pharmacological properties also remain largely unknown. Support vector machine classifiers were applied to UV-Visible spectra of liquid samples to obtain the following, color-based categories of tunillo fruits: A1-white, A2-red, A3-purple, and A4-orange. The spectrum of A2-red could be duplicated by combining those from A3-purple and A4-orange, while UPGMA-based hierarchical clustering of psbA-trnH and matK suggested that certain differences in color might actually have a genetic basis. The pigment quantification established A2-red and A3-purple as the most suitable candidates for the extraction of betalains and complex colored matrices, respectively. A2-red also had the highest content of phenols and flavonoids and displayed a noticeable anti-hyperglycemic effect.

Ethanolic extract and ethyl acetate fraction of Coutoubea spicata attenuate hyperglycemia, oxidative stress, and muscle damage in alloxan-induced diabetic rats subjected to resistance exercise training program.

Gentianaceae family (such as Coutoubea spicata) contains iridoids and flavonoids with antidiabetic properties. However, there is no information available about the antidiabetic effects of C. spicata when combined with resistance exercise training (RET). This study evaluated the effects of the ethanolic extract (EE) and ethyl acetate fraction (EAF) of C. spicata on biochemical markers, muscle damage, and oxidative stress in diabetic rats submitted to RET. Alloxan-induced diabetic rats were distributed into 4 groups (each group, n = 8) treated with distilled water (TD), EE, EAF, or metformin and submitted to RET. Two groups without the disease (each group, n = 8) (sedentary control and trained control), as well as a sedentary diabetic group (n = 8) were included. Body weight and glycemia were evaluated weekly. After 30 days, lipid/lipoprotein profile, aspartate aminotransferase, alanine aminotransferase, muscle damage ((creatine kinase (CK) and lactate dehydrogenase (LDH)), and oxidative stress (malondialdehyde (MDA), sulfhydryl groups (SH), and ferric reducing antioxidant power) were evaluated. MDA and SH for pancreas, liver, heart, and muscle were evaluated. C. spicata extract and fraction combined with RET recovered body weight and reduced glycemia, muscle damage (CK: 36.83% and 21.45%; LDH: 49.83% and 68.55%), and low-density lipoprotein cholesterol (70.63%; 59.18%) and improved redox status (MDA: 50.33%, 39.74%; and SH: 53.97%; 76.41%), respectively, when compared with the TD group. C. spicata plus RET promoted anti-hyperglycemic, lipid-reducing, and antioxidant effects in diabetic rats. Novelty C. spicata presents anti-hyperglycemic and lipid-lowering effects potentiated by RET. C. spicata reduces muscle injury and increases antioxidant defense.