Acute and chronic animal models for the evaluation of anti-diabetic agents.

Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential.

GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats.

AIM OF THE STUDY: This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents. MATERIALS AND METHODS: The GC-MS (Gas chromatography-mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. RESULTS: CTO (100 mg/kg and 200 mg/kg), cinnamaldehyde (20 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). CONCLUSION: Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity.

Assessment of Antiobesity Potential of Achyranthes aspera Linn. Seed.

The present study was designed to evaluate the quality control parameters, quantitative phytochemical analysis (total phenols, total flavonoids, and total saponin content), and the antiobesity effect of ethanol extract of Achyranthes aspera Linn. seed (EAA) by employing in vitro and in vivo models. In in vitro study, the inhibitory activity of EAA on pancreatic amylase and lipase was measured. The in vivo pancreatic lipase activity was evaluated by measurement of plasma triacylglycerol levels after oral administration of EAA along with lipid emulsion to Swiss albino mice. The EAA inhibited pancreatic amylase and lipase activity in vitro and elevations of plasma triacylglycerol level in mice. Furthermore, the antiobesity effect of EAA (900 mg/kg) was assessed in mice fed a high-fat diet with or without EAA for 6 weeks. EAA significantly suppressed the increase in body, retroperitoneal adipose tissue, liver weights, and serum parameters, namely; total cholesterol, total triglyceride, and LDL-cholesterol level. The anti obesity effects of EAA in high-fat-diet-treated mice may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic amylase and lipase activity. Histopathological effects of EAA on the liver of mice were also assessed.

Quality assessment and anti-obesity activity of Stellaria media (Linn.) Vill.

BACKGROUND: Obesity is recognized as a social problem, associated with serious health risks and increased mortality. Numerous trials have been conducted to find and develop new anti-obesity drugs through herbal sources to minimize side effects associated with the present anti-obesity drugs. The present study was designed to evaluate the quality control parameters, quantitative phytochemical analysis (total phenolic, total flavonoids and total saponin content), and the anti-obesity effect of lyophilized juice (LJ) of Stellaria media (Linn.) Vill. by employing in vitro and in vivo models. METHODS: In vitro studies were performed to evaluate the inhibitory activity of LJ on pancreatic amylase and lipase. The in vivo pancreatic lipase activity was evaluated by measurement of plasma triacylglycerol levels after oral administration of lipid emulsion to swiss albino mice. Furthermore, the anti-obesity effect of LJ was assessed at two doses, 400 mg/kg and 900 mg/kg body weight in mice fed a high-fat-diet with or without LJ for 6 weeks. RESULTS: The LJ inhibited pancreatic amylase and lipase activity in vitro and elevated plasma triacylglycerol level in mice. LJ suppressed the increase in body weight, retroperitoneal adipose tissue, liver weights and serum parameters viz., total cholesterol, total triglyceride, LDL-cholesterol level at the dose of 900 mg/kg body weight of the mice fed with high fat diet. The total phenolic, flavonoid and saponin contents were found to be 0.26 mg/g, 1.4 mg/g and 1.19 µg/g respectively of LJ. CONCLUSION: The anti-obesity effects of LJ in high-fat-diet fed mice may be partly mediated through delaying the intestinal absorption of dietary fat and carbohydrate by inhibiting digestive enzymes.

Hepatoprotective activity of Vitis vinifera root extract against carbon tetrachloride-induced liver damage in rats.

The ethanolic extract of the root of Vitis vinifera (Vitaceae) was evaluated for hepatoprotective activity in rats with liver damage induced by carbon tetrachloride. The extract at an oral dose of 200 mg/kg exhibited a significant protective effect by lowering the serum levels of SGPT, SGOT, alkaline phosphatase and total bilirubin. The extract at this dose also increases the level of total protein. These biochemical observations were supplemented by histopathological examination of liver sections. The activity of extract was also comparable to that of silymarin, a known hepatoprotective drug.

A review of chemistry and biological activities of the genus Aerva--a desert plant.

There are approximately 28 species of Aerva genus, but only a few species are medicinal of which A. persica, A. lanata and A. javanica are of great value. A number of flavonol glycosides (e.g., aervanone, kaempferol-3-galactoside, isorhamnetin-3-O-ß-D-glucoside) have been reported from Aerva persica as major phytoconstituents and the minor constituents are ß-cyanins (glycine betaine and trigonelline), sterols and carbohydrates. This plant is used as medicinal herb in several traditional systems of medicine all over the world, like diuretic, demulcent, purgative, emetic and tinder. Aerva plants are used to cure ulcer, lithiasis, dropsical affections, eye affection, toothache, headache, in disorders of abdomen and inflammation of internal organs. Roots and flowers are reported to possess hypoglycemic, antioxidant, anthelmintic, analgesic, antimalarial, antivenin activities and medicinal properties against rheumatism and kidney troubles.

Immunomodulatory potential of Nyctanthes abrortristis stem bark.

BACKGROUND: Phytotherapeutic modulation of the immune system to mitigate infectious ailments has been in vogue all over the world. OBJECTIVE: The present work has been designed to scientifically explore the immunomodulatory potential of Nyctanthes arbortristis stem bark using mice models. MATERIALS & METHOD: Methanolic (MNA) and aqueous (ANA) extracts of N. arbortristis stem bark were evaluated for possible modulation in humoral immunity through serum immunoglobulin estimation. The variation in cellular immunity was assessed using neutrophil adhesion test, carbon clearance assay, and cyclophosphamide-induced neutropenia. RESULTS AND DISCUSSION: Administration of MNA and ANA (both at 200 mg/kg, p.o.) significantly augmented the levels of serum immunoglobulins (humoral antibody), neutrophil adhesion, and phagocytic index (a measure of carbon clearance). Extracts also guarded the animals against cyclophosphamide-induced leukopenia, especially neutropenia. CONCLUSION: Results indicate that cellular and humoral immune responses were aroused by pretreatment of the animal with methanol and aqueous extract of N. arbortristis. Thus, the methanol and aqueous extract of N. arbortristis stem bark possesses a significant immunostimulant activity and can be used to uplift the immune system in the infectious condition.

Role of Dietary Supplements in Thyroid Diseases.

BACKGROUND: Thyroid hormones play a vital role in regulating our body's metabolism. Two important thyroid hormones released from the thyroid gland are tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid-stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although normally, the hormonal diseases cannot be cured, but we can improve their signs and symptoms using suitable dietary supplements. OBJECTIVE: The aim of the study was to thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in Hashimoto's thyroiditis; hyperthyroidism, as seen in Graves' disease; sick euthyroidism and subclinical hypothyroidism. METHODS: Literature was searched using the search terms "dietary supplements+thyroid diseases" on Pubmed, Google Scholar, Scopus, Cochrane Library, and other search engines, and data were collected from 1967 to November, 2021, including research inputs from the authors. The literature was thoroughly searched, and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. CONCLUSION: After analyzing various studies on this topic, we arrived at the conclusion that although there are various claimed and observed health benefits of dietary supplements in the prevention and treatment of various thyroid disorders, still several studies have shown too many risks to be associated with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status.

Plants and their Bioactive Compounds as a Possible Treatment for Traumatic Brain Injury-Induced Multi-Organ Dysfunction Syndrome.

BACKGROUND & OBJECTIVE: Traumatic brain injury is an outcome of the physical or mechanical impact of external forces on the brain. Thus, the silent epidemic has complex pathophysiology affecting the brain along with extracranial or systemic complications in more than one organ system, including the heart, lungs, liver, kidney, gastrointestinal and endocrine system. which is referred to as Multi-Organ Dysfunction Syndrome. It is driven by three interconnected mechanisms such as systemic hyperinflammation, paroxysmal sympathetic hyperactivity, and immunosuppression-induced sepsis. These multifaceted pathologies accelerate the risk of mortality in clinical settings by interfering with the functions of distant organs through hypertension, cardiac arrhythmias, acute lung injury, neurogenic pulmonary edema, reduced gastrointestinal motility, Cushing ulcers, acute liver failure, acute kidney injury, coagulopathy, endocrine dysfunction, and many other impairments. The pharmaceutical treatment approach for this is highly specific in its mode of action and linked to a variety of side effects, including hallucinations, seizures, anaphylaxis, teeth, bone staining, etc. Therefore, alternative natural medicine treatments are widely accepted due to their broad complementary or synergistic effects on the physiological system with minor side effects. CONCLUSION: This review is a compilation of the possible mechanisms behind the occurrence of multiorgan dysfunction and reported medicinal plants with organoprotective activity that have not been yet explored against traumatic brain injury and thereby, highlighting the marked possibilities of their effectiveness in the management of multiorgan dysfunction. As a result, we attempted to respond to the hypothesis against the usage of medicinal plants to treat neurodegenerative diseases.

In vitro antiplasmodial and antimicrobial potential of Tagetes erecta roots.

CONTEXT: Among strategies to combat malaria, the search for newer antimalarial compounds is a priority. Traditionally, Tagetes erecta Linn. (Compositae) has been used for the treatment of various diseases and ailments including malaria. OBJECTIVE: Five successive extracts (petroleum ether, chloroform, ethyl acetate, methanol and aqueous) of the roots of T. erecta and a new bithienyl compound, 2-hydroxymethyl-non-3-ynoic acid 2-[2,2']-bithiophenyl-5-ethyl ester from the roots of the plant, were evaluated for in vitro antiplasmodial activity against chloroquine sensitive and resistant strains of Plasmodium falciparum. The extracts were also tested for in vitro antimicrobial activity against seven microbial strains. MATERIALS AND METHODS: The antiplasmodial screening was carried out using the schizont maturation inhibition assay. Preliminary antimicrobial screening was carried out using the agar well assay followed by determination of minimum inhibitory concentration (MIC) using two-fold serial dilutions. RESULTS: Among all the extracts tested, the ethyl acetate fraction exhibited significant antiplasmodial efficacy with the 50% inhibitory concentrations (IC(50)) of 0.02 and 0.07 mg/mL against the chloroquine sensitive and resistant strains of Plasmodium falciparum respectively. The new bithienyl compound also showed significant schizonticidal activity against both chloroquine sensitive and resistant strains of Plasmodium falciparum with the IC(50) values of 0.01 and 0.02 mg/mL. Additionally, all extracts exhibited significant antimicrobial activity against three Gram-positive and two Gram-negative bacterial and two fungal strains with MIC values ranging between 12.5-100 µg/mL. DISCUSSION: The new bithienyl compound was profoundly able to arrest the ring stages of the malarial parasites thereby exerting its antiplasmodial effect. CONCLUSION: The observations provide support for the ethnobotanical use of the plant.

Lead Anti-Obesity Compounds from Nature.

BACKGROUND: Obesity has become a global issue, leading to increased risk of metabolic syndrome, which encompasses diabetes, cardiovascular disease, stroke, hypertension, and certain cancers. However, obesity is difficult to control through diet and exercise alone, as they are difficult to implement. OBJECTIVE: The objective of this review is to elucidate the active constituents that can be obtained from various natural sources that act as anti-obesity agents. Due to the global rise in the prevalence of obesity, an urgent need to prevent and control it has arisen. METHODS: For this review, we compiled information about natural anti-obesity products through an electronic search of the articles available via PubMed, Scopus, and other internet sources for the period 1975-2019 and included our own research. We analyzed and organized data on various natural products in popular use in addition to relevant pharmacognostic and biological studies. The products' mechanisms of action were also investigated. CONCLUSION: Consumption of diets that include high amounts of active anti-obesity natural compounds is a promising strategy for the suppression of lipid accumulation and adipogenesis in obese individuals.

Review on antioxidants and evaluation procedures.

Antioxidants are the substances that are capable of counteracting the damaging effects of the physiological process of oxidation occur in animal tissues. These may be nutrients (vitamins and minerals) as well as enzymes (proteins) in our body that assist in chemical reactions. They are believed to play a role in preventing the development of chronic diseases like cancer, diabetes, heart disease, stroke, Alzheimer's disease, rheumatoid arthritis, and cataracts etc. The present review article emphasizes on the various aspects of oxidants and antioxidants viz. definition, types, causes, mechanism, functions, adverse effects along with various in vivo and in vitro models of evaluation of antioxidant activity of new molecule, compounds or any plant or plant part. This review is one of its kinds which will be of great importance for researchers working in this area in search of antioxidant moieties and their biological evaluation.

Post-coital antifertility activity of Achyranthes aspera Linn. root.

Achyranthes aspera Linn. (Amaranthaceae) is an abundant indigenous herb in India. It is traditionally being used as an abortifacient. The ethanol extract of the root was screened for antifertility activity in proven fertile female albino rats at 200 mg/kg body weight and given orally on days 1-7 of pregnancy. The ethanol extract exhibited 83.3% anti-implantation activity when given orally at 200 mg/kg body weight. The rats, which continued their pregnancy, did not deliver any litters after their full term. Hence the combined antifertility (anti-implantation and abortifacient) activity of ethanol extract was 100%. The results suggest that the ethanol extract possess both anti-implantation and abortifacient activity. The ethanol extract also exhibited estrogenic activity tested in immature ovariectomised female albino rats. Histological studies were carried out to confirm this.

Anti-oxidant studies and anti-microbial effect of Origanum vulgare Linn in combination with standard antibiotics.

BACKGROUND: Origanum is one of the over 200 genera in the Lamiaceae (mint family), and this genus includes culinary, fragrant, and medicinal properties. The plant is reported to contain anti-microbial properties, but it lacks combination studies with that of synthetic antibiotics. AIM: To investigate the anti-oxidant and anti-microbial interaction studies of Origanum vulgare with standard drugs against Bacillus species of bacteria and Aspergillus niger. MATERIALS AND METHODS: The anti-oxidant properties of phenolic, non-phenolic fractions of chloroform extract and volatile oil were evaluated by free radical-scavenging, hydrogen peroxide radical-scavenging assay, reducing power, and metal chelating assays. RESULTS: The minimum inhibitory concentration and fractional inhibitory concentration index were determined which demonstrates the behavior of volatile oil, phenolic, and non-phenolic fractions of volatile oil with that of ciprofloxacin and fluconazole. The IC50 value for volatile oil was found to be 15, 30, and 30 µg/ml and that of phenolic fraction was 60, 120, and 120 µg/ml for free radical-scavenging, hydrogen peroxide-scavenging, and metal chelating assays respectively. Non-phenolic fraction was found to act antagonistically along with ciprofloxacin against B. cereus and B. subtilis, while the phenolic fraction exhibited indifferent activity along with ciprofloxacin against both the bacterial strains. CONCLUSION: This combination of drug therapy will not only prove effective in antibiotic resistance, but these natural constituents will also help in preventing body from harmful radicals which lead to fatal diseases.

Chemical composition of ethanol extract of Macrotyloma uniflorum (Lam.) Verdc. using GC-MS spectroscopy.

BACKGROUND: Macrotyloma uniflorum Linn (Fabaceae) is a herbaceous plant with annual branches. It is used in kidney stones, inflamed joints, fever, musculoskeletal disorders, sinus wounds and localized abdominal tumors. It is reported as an antioxidant and nutraceutical (forage and food). GC-MS analysis of ethanol extract has led to identification of twenty-eight compounds from M. uniflorum by comparison of their retention indices and mass spectra fragmentation patterns with those stored on the GC-MS computer library. RESULTS: The main constituents identified were mome inositol, ethyl alpha-d-glucopyranoside, n- hexadecanoic acid, linoleic acid (9, 12-octadecadienoic acid), its esters and ethyl derivatives, Vitamin E, stigmasterol and 3-beta-stigmast-5-en-3-ol. CONCLUSIONS: The extracts are rich in linoleic acid and its esters, mome inositol and ethyl alpha-d-glucopyranoside; therefore, this plant can be medicinally beneficial as an antioxidant, in diabetes and its related disorders.

Oreganum vulgare Linn. leaf: An Extensive Pharmacognostical and Phytochemical Quality Assessment.

PURPOSE: Standardization and detailed pharmacognostical studies of Oreganum vulgare Linn. leaf for authentication and commercial utilization. METHODS: Oreganum vulgare Linn. leaf was with standardization according to standard procedures described in WHO, 2011 and I.P. 1996. RESULTS: The physicochemical parameters total ash, acid insoluble ash, water soluble ash and sulphated ash were found to be 11.5%, 11%, 5, 10.5% w/w respectively. Foaming index was found be <100. The trace elements were found to be copper, lead, cadmium, zinc, cobalt, manganese, nickel and copper in ethanol extract and phytochemical screening of aqueous and ethanol extract showed the presence of carbohydrates, flavonoids, anthocyanins, phenolic compounds etc. CONCLUSION: The standardization parameters viz. physico-chemical parameters, macroscopy, microscopy, taxonomy, anatomy and preliminary phytochemical screening, microbial and aflatoxin count, HPTLC profile is being reported to help in authentication and development of monograph of this plant.

Screening of antidiabetic and antihyperlipidemic potential of oil from Piper longum and piperine with their possible mechanism.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and other symptoms like polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger) which ultimately causes various other complications like retinopathy, neuropathy, nephropathy and microangiopathy. OBJECTIVES: The antidiabetic and antihyperlipidemic potential of oil from Piper longum (PLO) and piperine was investigated with their possible mechanism using α-glucosidase, aldose reductase (AR), and pancreatic lipase inhibitory activity. METHODS: The biochemical parameters, viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride, and antioxidant parameters, were estimated for all treated groups in acute and chronic antihyperglycemic animal models. RESULTS: PLO (100 and 200 mg/kg), piperine (25 and 50 mg/kg), and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin, and high-density lipoprotein and decrease in glycosylated hemoglobin, triglyceride, and total plasma cholesterol in PLO-administered groups as compared to control group. The IC50 value of PLO for α-glucosidase, AR, and pancreatic lipase was found to be 150 ± 2.5, 120 ± 1.2, and 175 ± 1.2 µg/ml, respectively, which was found comparable with the standard drugs acarbose (90 ± 2.3 µg/ml), quercetin (80 ± 2.3 µg/ml), and orlistat (25 ± 0.5 µg/ml), respectively. CONCLUSION: The investigation done reveals that PLO has significant antidiabetic and antihyperlipidemic activity.

Combination Studies of Oreganum Vulgare Extract Fractions and Volatile Oil along with Ciprofloxacin and Fluconazole against Common Fish Pathogens.

PURPOSE: The study is aimed at finding new antibiotic therapy for aquaculture due to potential of bacteria to develop resistance to the existing therapies. Use of large quantities of synthetic antibiotics in aquaculture thus has the potential to be detrimental to fish health, to the environment and wildlife and to human health. METHODS: Antimicrobial potential of volatile oil and fractions of chloroform extract of Oreganum vulgare was evaluated alone and in the presence of standard antimicrobials against common fish pathogens by disc-diffusion, agar well assay and two fold microdilution method by nanodrop spectrophotometric method. RESULTS: The best results were represented by volatile oil followed by phenolic fraction by disc-diffusion, agar well and microdilution assays (Minimum inhibitory concentration). By the interaction studies, it was observed that the volatile oil and phenolic fraction were able to inhibit the pathogens at very low concentration compared to standard drugs. The fractional inhibitory concentration index (FICI) was calculated and volatile oil and phenolic fractions were found to be synergistic against Pseudomonas fluorescens and Candida albicans. CONCLUSION: The experimental data suggests the use of volatile oil and phenolic fraction in combination with standard antimicrobials to maintain healthy aquaculture with lesser adverse effects as compared to synthetic antibiotic therapy.