Extraction, purification, structural modification, activities and application of polysaccharides from different parts of mulberry.

The mulberry plant is a member of the Moraceae family and belongs to the Morus genus. Its entire body is a treasure, with mulberries, mulberry leaves, and mulberry branches all suitable for medicinal use. The main active ingredient in mulberries is mulberry polysaccharide. Studies have shown that polysaccharides from different parts of mulberry exhibit antioxidant, antidiabetic, antibacterial, anti-inflammatory, and blood pressure-lowering properties. There are more studies on the biological activities, extraction methods, and structural characterization of polysaccharides from different parts of mulberry. However, the structural characterization of mulberry polysaccharides is mostly confined to the types and proportions of monosaccharides and the molecular weights of polysaccharides, and there are fewer systematic studies on polysaccharides from different parts of mulberry. In order to better understand the bioactive structure of mulberry polysaccharides, this article discusses the recent research progress in the extraction, separation, purification, bioactivity, structural modification, and application of polysaccharides from different parts of mulberry (mulberry leaves, mulberry fruits, and mulberry branches). It also delves into the pharmacological mechanisms of action of mulberry polysaccharides to provide a theoretical basis for further research on mulberry polysaccharides with a view to their deeper application in the fields of feed and nutraceuticals.

Pharmaceutical Food Science: Search for Bio-Functional Molecules Obtained from Natural Resources to Prevent and Ameliorate Lifestyle Diseases.

In this review, our resent pharmaceutical food science research for bio-functional molecules obtained from natural resources that contribute to i) suppression of postprandial blood glucose elevation and/or improvement of glucose tolerance and ii) reduction of visceral fat accumulation and improvement of lipid metabolism were summarized. Based on studies using MONOTORI science, salacinol (1), neokotalanol (4), and trans-tiliroside (20) have been approved or notified by the Consumer Affairs Agency in Japan as functional substances in food with health claims, Food for Specified Health Use and Food with Functional Claims.

Extraction, Characterization, and In Vitro Hypoglycemic Activity of a Neutral Polysaccharide from the New Medicinal Mushroom Cantharellus yunnanensis (Agaricomycetes).

Polysaccharides serve as promising ingredients for health-beneficial functional foods, while there were no investigations into the structural characterizations and bioactivities of an edible mushroom Cantharellus yunnanensis. In the study, crude polysaccharides from this mushroom were extracted by hot water and isolated by ethanol precipitation. Then, a neutral polysaccharide (named CY-1) was purified from the crude polysaccharide by deproteinization with Sevag reagent, decolorization with a kind of macroporous adsorption resin SP-825, DEAE-52 cellulose column chromatography and dialysis. The physicochemical properties of CY-1 were characterized by UV, IR, SEM, NMR, and HPLC analyses. Structural characterizations revealed that CY-1 is a homogeneous heteropolysaccharide with an average molecular weight of 3.06 × 104 Da. CY-1 exhibited a honeycomb structure with an irregular branching shape, and it was composed of mannose, glucose, fucose, xylose, arabinose, galactose, rhamnose, and glucuronic acid, with molar fractions of 54.83%, 25.11%, 10.28% 4.53%, 2.12%, 1.64%, 0.83%, and 0.64%, respectively. In vitro hypoglycemic tests showed that CY-1 had an inhibitory effect on α-glucosidase. In addition, CY-1 of 160 µg/mL promoted glucose consumption in normal HepG2 cells. These results suggested that CY-1 may be a potential hypoglycemic agent.

Identification of α-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach.

The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC50 = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC50 = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC50 = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC50 = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified-three and two in NIM and PIM, respectively-as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds-dihydrocatalpol and leucosceptoside A-from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.

Extraction and Study of Hypoglycemic Constituents from Myrica rubra Pomace.

Myrica rubra pomace accounts for 20% of the fruit's weight that is not utilized when it is juiced. The pomace contains bioactive phenolic substances such as anthocyanins and flavonoids. To improve the utilization value of Myrica rubra pomace, an optimized extraction method for the residual polyphenols was developed using response surface methodology (RSM). The resulting extract was analyzed by high performance liquid chromatography (HPLC), and the in vitro hypoglycemic activity and antioxidant activity of the polyphenolic compounds obtained were also investigated. The optimum extraction conditions (yielding 24.37 mg·g-1 total polyphenols content) were: extraction temperature 60 °C, ultrasonic power 270 W, ethanol concentration 53%, extraction time 57 min, and solid to liquid ratio 1:34. Four polyphenolic compounds were identified in the pomace extract by HPLC: myricitrin, cyanidin-O-glucoside, hyperoside, and quercitrin. DPPH and hydroxyl radical scavenging tests showed that the Myrica rubra polyphenols extract had strong antioxidant abilities. It is evident that the residual polyphenols present in Myrica rubra pomace have strong hypoglycemic activity and the juiced fruits can be further exploited for medicinal purposes.

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.

Purification and characterization of hypoglycemic peptides from traditional Chinese soy-fermented douchi.

Douchi is a popular soy-fermented food that originated in China with documented hypoglycemic effects. However, the responsible molecules and the mechanism underlying their beneficial effects remain unclear. Therefore, in this study, we aimed to identify the responsible peptide(s) in douchi. A peptide extract of douchi was isolated step-wise by the C18 Sep-Pak technique, size exclusion chromatography, and semi-preparative liquid chromatography, and then the peptides were sequenced by UPLC-MS/MS. A total of 21 peptides were identified, of which three peptides, P3 (HPFR), P5 (VY), and P7 (SFLLR), were shown to improve glucose uptake in L6 cells. Both P5 and P7 increased glucose transporter 4 (GLUT4) translocation via the activation of AMPK and MAPK signaling pathways, but not the insulin-signaling pathway; adding an AMPK or an MAPK inhibitor prevented P5 or P7-induced glucose uptake as well as AMPK and MAPK activation. Our study showed that P5 and P7 could promote glucose uptake via AMPK and MAPK signaling pathways. In this study, two hypoglycemic peptides from douchi have been characterized for the first time.

Anti-diabetic activity of a sulfated galactoarabinan with unique structural characteristics from Cladophora oligoclada (Chlorophyta).

The polysaccharide from green alga Cladophora oligoclada, OHSS2, was a sulfated galactoarabinan which was constituted by a backbone of (1 â†’ 4)-ß-l-arabinopyranose units with partial sulfate at C-3 of (1 â†’ 4)-ß-l-arabinopyranose units. The side chains containing (1 â†’ 4)-ß-l-arabinopyranose, (1 â†’ 4)-ß-d-galactopyranose and/or (1 â†’ 4,6)-ß-d-galactopyranose units were in C-2/C-3 of (1 â†’ 4)-ß-l-arabinopyranose units. OHSS2 had strong anti-diabetic activity in vitro assessed by inhibition of human islet amyloid polypeptide (hIAPP) aggregation. The mechanism analysis of anti-diabetic activity showed that OHSS2 diminished the production of intracellular reactive oxygen species and alleviated hIAPP aggregation-induced oxidative stress in NIT-1 cells. OHSS2 stabilized mitochondrial membrane potential, and enhanced the mitochondrial complex I, II or III activity and ATP level. Thus, OHSS2 effectively protected mitochondria from hIAPP aggregation-induced damage. Furthermore, OHSS2 was co-localized with mitochondria and could have a direct influence on mitochondrial function. These results revealed that OHSS2 had potential as a novel anti-diabetic agent.

Hypoglycemic and hypolipidemic effects of Epigynum auritum in high fat diet and streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Epigynum auritum is mainly distributed in Southwest China, and has been used as a "dai" folk medicine with promising Besides, the leaves and barks of E. auritum have detoxifying, analgesic and relieving swelling effects. Previous studies evidenced that E. auritum was rich in pregnanes and their glycosides. However, the hypoglycemic and hypolipidemic effects of the extract from E. auritum (EAE) and its molecular mechanism are still not studied. AIM OF THE STUDY: The aim of this study is to investigate the hypoglycemic and hypolipidemic effects of EAE on high-fat diet and streptozocin-induced type 2 diabetic rats. MATERIALS AND METHODS: The high-fat diet and streptozocin induced type 2 diabetic model was established. The diabetic rats were treated with 70% ethanol extract of E. auritum (100 and 300 mg/kg/d) or metformin (DMBG, 100 mg/kg/d) every day for 4 weeks. Fasting blood glucose was recorded weekly. The phenotypic changes were evaluated by the measurement of biochemical indexes and immunohistochemical. The expressions of signaling-related proteins were explored by western blotting. RESULTS: EAE could effectively regulate the metabolism of glucose and lipids in diabetic rats by increasing insulin sensitivity. In addition, EAE ameliorated the oxidative stress damage and further mitigated the liver, kidney, and pancreatic damage. Mechanism research results show that EAE treatment increased the phosphorylation of Akt, AMPK and GSK-3ß, up-regulated the expression of GLUT-2, GLUT-4 and PPAR-α, and reduced PPAR-γ and FAS expressions. CONCLUSION: EAE exhibited significant hypoglycemic and hypolipidemic effects in HFD/STZ-induced diabetes rats. The mechanism may be related to the effective upregulation of AMPK/Akt/GSK-3ß pathway and the decreased expression of PPAR-γ and FAS. It could be a promising natural product with potential value for the development of drugs to prevent or treat type 2 diabetic.

Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020.

BACKGROUND: In traditional herbal medicine, the Gymnema species has been well known for various therapeutic activities such as anti-diabetic, anti-inflammatory, anti-bacterial, anti-arthritic, anti-hyperlipidemic, cytotoxic, and immunostimulatory activities. This review is an effort to analyse all the recent studies done to explore the anti-diabetic potential of traditional Gymnema species. Gymnema sylvestre (Retz.) R.Br. ex Sm. is an important member of the Apocynaceae family that has been used to treat a variety of diseases, the most studied of which is diabetes. This action is mostly due to the pharmacologically active phytoconstituents present in its extract, which include gymnemic acids, triterpenoid saponin glycosides, and so on. Numerous other Gymnema species have also demonstrated a similar pharmacological action. INTRODUCTION: The goal of this study is to give a critical overview of the available data on Gymnema species that are used to treat diabetes. The major goal of this study is to give up-to-date knowledge on ethnopharmacology, botany, pharmacology, and structure-activity relationships of Gymnemaspecies from 2016 to 2020, as well as potential future research. The potential of using medicinal plants for alleviating symptoms of diabetes is recently being recognized. This review aims to summarize the available data and highlight both the potential and shortcomings of using Gymnema therapeutically. This knowledge can further be used to develop more therapeutically effective drugs derived from Gymnema. MATERIALS AND METHODS: Data for Gymnema species was obtained using a mix of several search terms from online databases such as PubMed, SCOPUS, and Europe PMC. Other literature surveys relevant to traditional knowledge, phytochemistry, pharmacology, or structure-activity relationship activity were also used as reference. Several methods by which Gymnema species extracts exert their effects have been investigated, and a summary of the newly discovered chemicals isolated from the plant in the previous five years has been provided. RESULTS: SAR based evaluation has been carried out for a total of 27 pharmacologically active compounds belonging to three species of Gymnema genus (Gymnema sylvestre, Gymnema latifolium, and Gymnema inodorum).These compounds demonstrated the critical significance of plant medicines for diabetes management. Numerous heterocyclic compounds have anti-diabetic action and may serve as a starting point for the design and identification of new diabetes inhibitors. CONCLUSIONS: This study aims to provide researchers with a better understanding of the antidiabetic potential Gymnema species, as well as an outline of prospective future developments. It was concluded after studying the evaluation done in the last 5 years that although extracts of Gymnema have shown good antidiabetic potential, further modifications in the structures could result in the development of more potent and safer compounds.

Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination.

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.

Insulin discovery: A pivotal point in medical history.

The discovery of insulin in 1921 - due to the efforts of the Canadian research team based in Toronto - has been a landmark achievement in the history of medicine. Lives of people with diabetes were changed forever, considering that in the pre-insulin era this was a deadly condition. Insulin, right after its discovery, became the first hormone to be purified for human use, the first to be unraveled in its amino acid sequence and to be synthetized by DNA-recombinant technique, the first to be modified in its amino acid sequence to modify its duration of action. As such the discovery of insulin represents a pivotal point in medical history. Since the early days of its production, insulin has been improved in its pharmacokinetic and pharmacodynamic properties in the attempt to faithfully reproduce diurnal physiologic plasma insulin fluctuations. The evolution of insulin molecule has been paralleled by evolution in the way the hormone is administered. Once-weekly insulins will be available soon, and glucose-responsive "smart" insulins start showing their potential in early clinical studies. The first century of insulin as therapy was marked by relentless search for better formulations, a search that has not stopped yet. New technologies may have, indeed, the potential to provide further improvement of safety and efficacy of insulin therapy and, therefore, contribute to improvement of the quality of life of people with diabetes.

Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. AIM OF THE STUDY: This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. MATERIALS AND METHODS: The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-κB signaling pathway in GLUTag cells. RESULTS: Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-κB pathway. Notably, isoquercitrin exhibited more pronounced anti-diabetic efficacy. CONCLUSIONS: The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-κB pathway.

Integrated molecular biology and metabonomics approach to understand the mechanism underlying reduction of insulin resistance by corn silk decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Corn silk is composed of the style and stigma of Zea mays L. Its medical value was first reported in "Southern Yunnan Materia Medica" in the Ming Dynasty. It was considered to be a heat-clearing and diuretic drug. In "Zhejiang Folk Herbal Medicine," the following has been reported: "Corn silk needs one liang. Decoction in water can cure diabetes." Recent studies have shown that corn silk can lower blood sugar levels; however, to date, corn silk has undergone simple pharmacodynamic evaluations, with both its degree and mechanism of action remaining unclear. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of corn silk, with respect to having antioxidative ability, reducing insulin resistance, and having a hypoglycemic effect. MATERIALS AND METHODS: In this study, a type 2 diabetes mellitus (T2DM) rat model was established via a high sugar and high fat diet combined with streptozotocin (35 mg/kg) administration. Wistar rats were administered corn silk decoction and metformin via gavage for four weeks, and the fasting blood glucose (FBG) and body weight were measured every two weeks. After the experiment, the insulin level, insulin index, and glycogen content were determined. Hematoxylin-eosin staining was used to observe the morphological changes of the skeletal muscle tissue in rats. The levels of malondialdehyde and superoxide dismutase in the serum and skeletal muscle were detected, and the mRNA content and protein levels of key proteins in the JNK-IRS-GLUT4 signaling pathway were determined using real-time quantitative polymerase chain reaction and western blotting. Then, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, combined with multiple statistical analyses, was used to identify potential biomarkers in the serum of T2DM rats, for determining the key metabolic pathways responsible for the action of corn silk. RESULTS: The results showed that corn silk could reduce FBG, insulin level, and glycogen content in T2DM rats; reduce the level of oxidative stress in serum and skeletal muscle; restore the pathological structure of skeletal muscle; inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate (IRS) in skeletal muscle; and upregulate the expression of glucose transporter type 4 (GLUT4) for transport of glucose and to reduce insulin resistance. Moreover, metabonomic analysis elucidated that corn silk could significantly affect 26 biomarkers (such as pentosidine, palmitic acid, lysoPC, and p-Cresol sulfate) and metabolic pathways (such as phenylalanine metabolism, phospholipid metabolism, bile acid metabolism, and biosynthesis of unsaturated fatty acids). CONCLUSION: The interaction between endogenous metabolites and proteins in signaling pathways was analyzed using metabonomics and molecular biology methods. Corn silk inhibited JNK-IRS-GLUT4 signal transduction in skeletal muscle via antioxidative effects, by increasing the sensitivity of peripheral tissue to insulin, by reducing insulin resistance, and through hypoglycemic effects.

Diaphragma juglandis extracts modifies the gut microbiota during prevention of type 2 diabetes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The diaphragma juglandis (DJ) comes from the wooden septum in the core of Juglans regia L, also known as the walnut septum. In Iranian traditional medicine, walnut distraction wood was widely used in the treatment of diabetes. However, there is a lack of research data on the mechanism of DJ against diabetes. AIM OF THE STUDY: To explore the protective effect of diaphragma juglandis extract (DJE) on type 2 diabetic rats and the hypoglycemic mechanism of DJE. MATERIAL AND METHODS: Supplemented DJE and fed a high-fat diet for five weeks, and then injected low-dose STZ, successfully induced type 2 diabetic rats. Collected rat serum, liver, pancreas and feces to determine the biochemical parameters of serum and liver, analyze the pathological damages of pancreas and liver, and measure the changes of gut microbes in feces. RESULTS: DJE could inhibit the metabolic abnormalities of T2DM by improving insulin resistance, abnormal lipid metabolism, liver damage, oxidative stress, and reducing inflammation. DJE significantly held fasting blood glucose, glycosylated serum protein, serum low density lipoprotein, high density lipoprotein, oral glucose tolerance test, nitric oxide, superoxide dismutase and catalase, serum and liver triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, lipopolysaccharide, fasting insulin and tumor necrosis factor-α and prevented the pathological damage of pancreas and liver. The 16SrRNA gene sequencing results showed that DJE intercepted the disorders of the fecal gut microbes, mainly including Lactobacillaceae, Rikenella, Pygmaiobacter, Oscillospiraceae and Klebsiella. Spearman correlation analysis showed that the changes of gut microbes were closely relative with biochemical parameters. CONCLUSION: DJE might prevent type 2 diabetes and its complications and hold up the disorders of gut microbes.

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.

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.

Comparison of the Efficiency of Lepidium sativum, Ficus carica, and Punica granatum Methanolic Extracts in Relieving Hyperglycemia and Hyperlipidemia of Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose levels that occurs either due to insufficient insulin production or mounting resistance to its action. The purpose of this study was to investigate if methanolic extracts of Lepidium sativum seeds, Ficus carica, and Punica granatum leaves had any effect on blood sugar levels in normal and streptozotocin (STZ) diabetic rats, as well as to explore the most effective extract. METHOD: Healthy male albino rats weighing 185-266 g were divided into nine groups of eight rats each: normal control, diabetic control, diabetic rats with dietary supplements of L. sativum, F. carica, and P. granatum methanolic extracts, and diabetics treated with insulin. All of the rats were fed on ordinary diet with nutritional pellets and were given water ad libitum. To induce diabetes, all animals were administered with STZ intraperitoneal injection at a dose of 60 mg/kg body weight. For five weeks, the crude plant extracts were given orally to various groups of rats at doses of one hundred and two hundred mg/kg body weight. After that, animal groups were sacrificed and blood samples were taken. RESULTS: Phytochemical analysis revealed that the highest amounts of polyphenolic compounds were present in L. sativum seeds and P. granatum leaves, while leaves of F. carica showed the highest amounts of alkaloid and flavonoid content compared to other extracts. Oral administration of F. carica and L. sativum extracts at the dosage of 100 and 200 mg/kg significantly reduced glucose, lipid profile, kidney, and liver enzyme levels. A significant increase in HbAlc levels was also observed with L. sativum extract at a dose of 200 mg/kg compared to diabetic controls. Mellitus rats supplemented with 100 and 200 mg/kg methanolic extracts of P. granatum had higher serum triglycerides and lower serum low-density lipoprotein cholesterol (LDL-C) than normal control rats. F. carica extract is more effective than L. sativum and P. granatum extracts in the prevention and control of type 2 diabetes mellitus (T2DM) and its consequences.

Natural products embedded crown ethers as potent insulin secretory agents.

Natural products embedded crown ethers were prepared by utilizing bioactive natural products including chrysin, tetrahydroisoquinoline (THIQ), and biochanin-A. The prepared crown ether scaffolds were evaluated and compared with their natural product precursors for insulin secretory activity on isolated mice islets and for their fluorescent properties. All the crown adducts were found more active as compared to their natural product precursors. Bischrysin 32-crown-10 (6d), THIQ 15-Crown-5 (6a) and chrysin 16-crown-5 (6c) showed mild, moderate and strong insulin secretory activity, respectively when compared with the standard drug tolbutamide (TB). Particularly crown derivative 6c showed strong activity (31.10 ng/islet/h) that is almost two (02) fold higher than that of standard drug TB (16.82 ng/islet/h). To the best of our knowledge crown ethers based antidiabetic study is being reported for the first time in literature through this work. Furthermore, fluorescence study showed the significant increase in absorption and emission maximum (hypsochromic effect) in crown structures when compared with their natural product precursors. Present optimistic results obtained from this study may be a guided template for developing new effective insulin secretory agents.

Aquilaria Species (Thymelaeaceae) Distribution, Volatile and Non-Volatile Phytochemicals, Pharmacological Uses, Agarwood Grading System, and Induction Methods.

Agarwood is a highly valuable fragrant wood of Aquilaria spp. (Thymelaeaceae) which has been widely utilized in traditional medicine, religious rites, and cultural activities. This study summarizes a review on the identification of Aquilaria cultivars, volatile and non-volatile phytochemicals, pharmacological uses, and agarwood grading system to determine its quality, and different agarwood induction methods. Due to the highly demanding and depleted natural resources, the research on agarwood is still insufficient, and it has broad research and development prospects in many industries. However, due to the significant scientific nature of agarwood application, developing high-quality products and drugs from agarwood have become highly important, while no one has discussed in detail the phytochemicals uses and provided a summary until now. The main phytochemicals of agarwood include terpenoids, dominated by sesquiterpenes. For centuries, terpenoids have been used in traditional Chinese medicine and have been shown to possess various pharmacological properties, including bacteriostatic, antibacterial, sedation, analgesia, anti-inflammation, anti-asthmatic, hypoglycemic, antidepressant, and many others. Alongside biological activity screening, phytochemical advances and pharmacological research have also made certain progress. Therefore, this review discusses the research progress of agarwood in recent years and provides a reference basis for further study of Aquilaria plants and agarwood.