Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.

Phytochemistry and Therapeutic Potential of Cupressus torulosa Needles Essential Oil from India.

Cupressus torulosa is an evergreen tree with a wide distribution in north-western Himalayan region of India. Its needles have long been used in traditional medicine for anti-inflammatory, antimicrobial, and wound-healing properties. This study aimed to scientifically validate the traditional claim of the needles to treat inflammation by evaluating the chemical composition, antioxidant potential, and anti-inflammatory activity of the essential oil extracted from the needles (CTEO) using hydro-distillation. Qualitative and quantitative chemical composition of the CTEO was determined with the aid of GC-MS and GC-FID techniques. The major constituents of the CTEO were terpinen-4-ol (393.8±12.5 µg/mg), totarol (55.0±17.2 µg/mg), and sabinene (43.7±2.8 µg/mg). CTEO exhibited significant antioxidant activity when evaluated using DPPH free radical scavenging and reducing power assays. Furthermore, the CTEO demonstrated good anti-inflammatory behavior in in vitro egg albumin denaturation assay, with an IC50 of 27.32 µg/mL. In vivo tests using carrageenan-induced paw edema and xylene-induced ear edema in rats showed significant effects at doses of 30 mg/kg for up to 1 hour. The significant discoveries not only support the established assertions about the anti-inflammatory properties of C. torulosa needles but also highlight their potential as a useful resource in the growing herbal, complementary, and alternative medicine sectors.

Protein Expression and Bioinformatics Study of Granulosa Cells of Polycystic Ovary Syndrome Expressed Under the Influence of DHEA.

Background: The reproductive system is heavily dependent on ovarian follicles, which are made up of germ cells (oocytes) and granulosa cells (GCs), including cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Understanding their normal and steroid-induced functions is the key to understanding the pathophysiology of endocrinal diseases in women. Objective: This study investigated the differentially expressed proteins by CGCs and MGCs of patients with polycystic ovarian syndrome (PCOS) and without subsequent exposure to dehydroepiandrosterone sulfate (DHEAS) and functional differentiation. Design: The present study was observational and experimental study carried out in hospital involving 80 female patients undergoing IVF for infertility. Methods: In this study, we isolated CGCs and MGCs from the follicular fluid of both PCOS and non-PCOS patients undergoing in vitro fertilization (IVF). The cells were cultured and treated with DHEAS for 48 hours, and these cells were extracted, digested, and analyzed by tandem mass spectrometry followed by processing of the results using open-source bioinformatics tools. Results: The present investigation discovered 276 and 341 proteins in CGCs and MGCs, respectively. DHEAS reduced the number of proteins expressed by CGCs and MGCs to 34 and 57 from 91 and 94, respectively. Venn results of CGCs revealed 49, 53, 36, and 21 proteins in normal CGCs, PCOS-CGCs, post-DHEAS, and PCOS-CGCs, respectively. Venn analysis of MGCs showed 51 proteins specific to PCOS and 29 shared by normal and PCOS samples after DHEAS therapy. MGCs express the most binding and catalytic proteins, whereas CGCs express transporter-related proteins. A protein pathway study demonstrated considerable differences between normal and PCOS samples, while DHEAS-treated samples of both cell lines showed distinct pathways. String findings identified important network route components such as albumin, actin, apolipoprotein, complement component C3, and heat shock protein. Conclusion: This is the first study to show how DHEAS-induced stress affects the expression of proteins by MGCs and CGCs isolated from normal and PCOS patients. Further studies are recommended to identify PCOS biomarkers from CGCs and MGCs expressed under the influence of DHEAS.

Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model.

Background: Tinosopora cordifolia (Willd) (TC) is commonly used in Ayurvedic medicine since long time for number of ailments and its preparations are also considered by food safety and standards authority of India as nutritional supplement. However the scientific evidence on its possible safety and efficacy in polycystic ovarian syndrome and associated complications was not studied in detail. Objectives: The purpose of this investigation is to examine whether or not TC can have therapeutic effects on letrozole induced PCOS and related complications such as body weight, dyslipidaemia, glucose tolerance, hormonal regulation, insulin resistance and sensitivity, severity of PCOS and histopathological changes in ovary using mice animal model. Design: Present study is a preclinical study involving laboratory animals. Methods and analysis: After verifying the absence of PCOS, the animals began receiving Letrozole, which lasted for 21 days. Fasting blood glucose (FBG), the oral glucose tolerance test (OGTT), triglycerides, cholesterol, and weight were recorded. The levels of hormones like oestrogen, progesterone, insulin, testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH), histopathology was carried out. Ethics: The Institutional Animal Ethics Committee at DITU gave its clearance to the animal experimentation on July 10, 2021 (DITU/IAEC/21-22/07-06). Discussion: The majority of cornified epithelial cells were seen in groups treated with TC extract during the estrous phase of the cycle. Mice exposed to TC retained normal body weight. FBG, 1- and 2-hour OGTT, triglyceride and cholesterol levels were all significantly improved by extracts. Estradiol, progesterone, testosterone, insulin, LH and FSH concentration were all corrected in TC-treated animals. The HOMA-IR, HOMA-Beta and QUICKI values were also corrected with TC extracts. The morphological and microscopic features of the ovary were also greatly enhanced. Based on these findings, we conclude that treating PCOS mice with TC extracts significantly ameliorates the disease and severity down to nil-to-moderate levels by reducing hyperinsulinemia, hyperandrogenism, dyslipidaemia, enhancing insulin sensitivity, correcting oestrogen, progesterone, LH and FSH levels via enhanced ovarian function. Further molecular and cellular level of study is recommended for further elaboration of mechanism of action. Plain language summaries: • Tinospora cordifolia satva, oil and hydroalcoholic extract were studied in letrozole-induced PCOS in mice model• Anti PCOS efficacy of 3 preparations studied with respect to their mechanism of action in detail• For the first time proposing method of calculating severity of PCOS in animal model• Tinospora cordifolia oil preparation completely reversed PCOS effect of letrozole and made them normal• Histopathological and morphological studies support the biochemical claims.

Antioxidant Properties Mediate Nephroprotective and Hepatoprotective Activity of Essential Oil and Hydro-Alcoholic Extract of the High-Altitude Plant Skimmia anquetilia.

There are many high-altitude plants such as Skimmia anquetilia that are unexplored for their possible medicinal values. The present study was conducted to examine the antioxidant activities of Skimmia anquetilia (SA) using in vitro and in vivo models. The SA hydro-alcoholic extracts were investigated using LC-MS for their chemical constituents. The essential oil and hydro-alcoholic extracts of SA were evaluated for pharmacological properties. The antioxidant properties were evaluated using in vitro DPPH, reducing power, cupric reducing antioxidant power, and metal chelating assays. The anti-hemolytic activity was carried out using a human blood sample. The in vivo antioxidant activities were evaluated using CCL4-induced hepatotoxicity and nephrotoxicity assay. The in vivo evaluation included histopathological examination, tissue biochemical evaluation such as the kidney function test, catalase activity, reduced glutathione activity, and lipid peroxidation estimation. The phytochemical investigation showed that the hydro-alcoholic extract contains multiple important active constituents such as L-carnosine, acacetin, linoleic acid, leucylleucyl tyrosine, esculin sesquihydrate, etc., similar to the components of SA essential oil reported in a previous study. The high amount of total phenolic content (TPC) and total flavonoid content (TFC) reflect (p < 0.001) a high level of reducing power, cupric reducing, and metal chelating properties. This significantly (p < 0.001) inhibited enlargement of the liver, with a significant reduction in ALT (p < 0.01) and AST (p < 0.001). Highly significant improvement in the functioning of the kidney was noted using the blood urea and creatinine (p < 0.001) levels. Tissue-based activities showed a major rise in catalase, reduced glutathione, and reduced lipid peroxidation activities. We conclude from this study that the occurrence of a high quantity of flavonoid and phenolic contents had strong antioxidant properties, leading to hepatoprotective and nephroprotective activity. Further active constituent-specific activities should be evaluated.

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia.

Background: The plant Tinospora cordifolia (TC), traditionally known as guduchi or giloy, is used for a number of health conditions as a nutritional supplement and rejuvenation medicine. Its nutritional supplementary products are traditionally recommended for a wide range of health issues, including diabetes, menstruation discomfort, fever, obesity, inflammation, and more. Unfortunately, there has not been extensive research into its effectiveness in treating or managing insulin resistance, lipid and carbohydrate metabolism, hormonal imbalance, and metabolic syndrome-associated polycystic ovary syndrome (PCOS). Methods: Consequently, the present study was designed to induce insulin resistance, dyslipidemia, hormonal abnormality, hyperglycemia, and menstrual disturbance of PCOS using dehydroepiandrosterone (DHEA) in mice and study the effect of oral TC extracts on these factors by using ancient and modern technologies. During the 21-day study, 6 mg/100 g/day of DHEA was given to female mice. Levels of glucose, insulin, lipids, and hormones were estimated. In addition to being seen with the naked eye, the morphological and microscopic changes were also observed on histology slides. Results: The study outcomes show that pretreatment with TC preparations significantly improved biochemical and histological abnormalities in female mice. Diestrus phase was only observed in DHEA-treated animals, while cornified epithelial cells were present in TC-treated mice. Pretreatment with TC satva showed significant (p < 0.001) reductions in body weight compared to placebo. Fasting blood glucose, 1-h OGTT, and 2-h OGTT levels were all significantly lower in TC satva- and oil-treated animals in comparison to the disease control group (p < 0.001). Treatment with TC extracts resulted in a normalization of estradiol, progesterone, and testosterone levels (p < 0.05). Treatment with TC extract improved lipid profiles (p < 0.001), LH/FSH ratios (p < 0.01), fasting insulin levels (p < 0.001), HOMA-IR (p < 0.001), HOMA-Beta (p < 0.001), and QUICKI (p < 0.001). Both macroscopic and microscopic alterations were seen to be restored after TC extract treatment. After being treated with TC satva, oil, and hydroalcoholic extract, the severity of PCOS decreased by 54.86%. Conclusions: These findings lead us to the conclusion that TC extracts and satva as nutritional supplements are useful for treating PCOS and associated symptoms. It is recommended that additional research be conducted to determine the molecular mechanism of action of TC nutritional supplements on PCOS-related changes in metabolic profiles. We also recommend further clinical studies to explore the clinical efficacy and effectiveness of TC nutritional supplements in treating and/or managing PCOS.

Impact of Medical Conditions and Medications on Road Traffic Safety.

OBJECTIVES: Many medical conditions and medicines with therapeutic importance have been shown to impair driving skills, causing road traffic accidents, which leads to great human and economic suffering in Oman. The primary purpose of this study was to assess retrospectively the extent of medical conditions and medications influencing road traffic safety among drivers involved in road accidents. METHODS: We conducted a retrospective study among 951 injured or non-injured drivers who reported to Khoula and Nizwa hospitals. We used the Al-Shifa database to find the drivers and contacted randomly selected patients over phone. RESULTS: The majority of victims were male (72.0%), involving personal cars, and reported at Khoula Hospital. The results show that 7.6% of the victimized drivers had a history of medical conditions with diabetes and hypertension (36.1% each) the most common. About 4.0% of victims were on medications of which insulin was the most common (9.4%). Loss of control was contributed to 38.5% of cases followed by dizziness (25.6%), sleep amnesia (10.3%), and blurred vision (7.7%). Other effects blamed by victimized drivers include vertigo, phonophobia, photophobia, back pain, loss of sensation, and headache accounting for 17.9% of cases. CONCLUSION: Medical conditions and medications influence road traffic safety to some extent in Oman.

Anthropometric and body composition analysis of infertile women with polycystic ovary syndrome.

OBJECTIVES: To evaluate the body composition and anthropometric profile of infertile women who have been diagnosed with polycystic ovary syndrome (PCOS) and to investigate the incidence of PCOS and to examine body fat composition as a risk factor for this disease. METHODS: This hospital-based case controlled study was conducted on a cohort of 132 patients with and without PCOS. Bioelectrical impedance analysis was used to record body composition parameters, such as total body fat, visceral fat, subcutaneous fat, skeletal muscle composition and their distribution in the trunk, legs and arms, as well as blood pressure. Anthropometric profile parameters, including body mass index (BMI), ideal body weight (IBW), waist circumference, hip circumference and waist-to-hip ratio, were also recorded. RESULTS: The mean age of incidence of PCOS was 29.74 ± 3.32 years (OR 1.417), and most of the cohort exhibited high to very high visceral fat with significant correlation (p < 0.001). Total body fat distribution and whole, trunk, arm and leg subcutaneous fat were significantly higher in patients with PCOS (p < 0.001). The mean BMI, waist and hip circumference of the PCOS group were 28.2 ± 6.08, 97.44 ± 15.11 cm and 109.22 ± 17.39 cm, respectively. The results also indicated significant increases in DP and MAP (OR 1.528) in patients with PCOS compared to the control group (p < 0.001). CONCLUSION: This study exhibits higher levels of BMI, body fat distribution, waist and hip circumference, diastolic and mean blood pressure, visceral fat, and a disproportionate increase in the level of global fat and its distribution.

Risk Factors and Plasma Glucose Profile of Gestational Diabetes in Omani Women.

OBJECTIVES: We sought to conduct a detailed study on the risk factors of gestational diabetes mellitus (GDM) in Omani women to determine the actual and applicable risk factors and glucose profile in this population. METHODS: We conducted a cross-sectional case-control study using pregnant women diagnosed with GDM. Pregnant women without GDM were used as a control group. We collected information related to age, family history, prior history of pregnancy complications, age of marriage, age of first pregnancy, fasting glucose level, and oral glucose tolerance test (OGTT) results from three hospitals in Oman through face-to-face interviews and hospital records. RESULTS: The median age of women with GDM was 33 years old (p < 0.050). A significant risk was noted in women with a history of diabetes (p < 0.001), and those with mothers' with a history of GDM. A significant (p < 0.010) relationship with a likelihood ratio of 43.9 was observed between the incidence of GDM in women with five or six pregnancies, a history of > 3 deliveries, height < 155 cm, and pregnancy or marriage at age < 18 years (p < 0.010). The mean difference in random plasma glucose, one-hour OGTT, and two-hour OGTT was significantly higher in GDM cases compared to control. CONCLUSIONS: Glucose profile, family history, anthropometric profile, and age of first pregnancy and marriage should be considered while screening for GDM and determining the care needs of Omani women with GDM.

Interventions by pharmacists in out-patient pharmaceutical care.

Interventions by the pharmacists have always been considered as a valuable input by the health care community in the patient care process by reducing the medication errors, rationalizing the therapy and reducing the cost of therapy. The primary objective of this study was to determine the number and types of medication errors intervened by the dispensing pharmacists at OPD pharmacy in the Khoula Hospital during 2009 retrospectively. The interventions filed by the pharmacists and assistant pharmacists in OPD pharmacy were collected. Then they were categorized and analyzed after a detailed review. The results show that 72.3% of the interventions were minor of which 40.5% were about change medication order. Comparatively more numbers of prescriptions were intervened in female patients than male patients. 98.2% of the interventions were accepted by the prescribers reflecting the awareness of the doctors about the importance of the pharmacy practice. In this study only 688 interventions were due to prescribing errors of which 40.5% interventions were done in changing the medication order of clarifying the medicine. 14.9% of the interventions were related to administrative issues, 8.7% of the interventions were related to selection of medications as well as errors due to ignorance of history of patients. 8.2% of the interventions were to address the overdose of medications. Moderately significant interventions were observed in 19.4% and 7.5% of them were having the impact on major medication errors. Pharmacists have intervened 20.8% of the prescriptions to prevent complications, 25.1% were to rationalize the treatment, 7.9% of them were to improve compliance. Based on the results we conclude that the role of pharmacist in improving the health care system is vital. We recommend more number of such research based studies to bring awareness among health care professionals, provide solution to the prescription and dispensing problems, as it can also improve the documentation system, emphasize the importance of it, reduce prescribing errors, and update the knowledge of pharmacists and other health care professionals.

Hypoglycemic Effect of Calotropis gigantea Linn. Leaves and Flowers in Streptozotocin-Induced Diabetic Rats.

OBJECTIVES: To evaluate the hypoglycemic and anti-diabetic activity of chloroform extract of Calotropis gigantea leaves and flowers in normal rats and streptozotocin induced diabetes. METHODS: The hypoglycemic activity in normal rats was carried out by treatment using chloroform extract of Calotropis gigantea leaf and flower 10, 20 and 50 mg/kg, orally. The oral glucose tolerance test was carried out by administering glucose (2 g/kg, p.o), to non-diabetic rats treated with leaf and flowers extracts at oral doses 10, 20 and 50 mg/kg, p.o and glibenclamide 10 mg/kg. The serum glucose was then measured at 0, 1.5, 3 and 5 hr after administration of extracts/drug. Streptozotocin-induced diabetic rats were administered the same doses of leaf and flower extracts, and standard drugs glibenclamide was given to the normal rats or 0.5 ml of 5% Tween-80, for 27 days. The blood sample from all groups collected by retro-orbital puncture on 7, 14, 21 and 27th days after administration of the extracts/drug and used for the estimation of serum glucose levels using the glucose kit. RESULTS: The Calotropis gigantea leaves and flowers extracts were effective in lowering serum glucose levels in normal rats. Improvement in oral glucose tolerance was also registered by treatment with Calotropis gigantean. The administration of leaf and flower extracts to streptozotocin-induced diabetic rats showed a significant reduction in serum glucose levels. CONCLUSION: It is concluded that chloroform extracts of Calotropis gigantea leaves and flowers have significant anti-diabetic activity.

Studies on anti-diarrhoeal activity of Calotropis gigantea R.Br. in experimental animals.

PURPOSE: Calotropis gigantea R. Br. (Asclepiadaceae) a wildly growing plant has been reported to possess number of medicinal properties and other purposes. The purpose of the present study was to evaluate scientifically the anti-diarrheal effects of C. gigantea used traditionally in Indian system of medicine using castor oil-induced diarrhoea model. METHODS: The anti-diarrheal effect of hydroalcoholic (50:50) extract of aerial part of Calotropis gigantea was studied against castor oil-induced-diarrhea model in rats. The gastrointestinal transit rate was expressed as the percentage of the longest distance traversed by the charcoal divided by the total length of the small intestine. The weight and volume of intestinal content induced by castor oil were studied by enteropooling method. RESULTS: Like atropine (3 mg/kg, i.p.) there were significant reductions in fecal out put and frequency of droppings when the plant extracts of 200 and 400 mg/kg doses were administered intraperitoneally compared with castor oil treated rats. All doses of the plant extracts also significantly retarded the castor-oil induced enteropooling and intestinal transit. The dose 100 (P<0.01), 200 and 400 mg/kg significantly inhibited (P<0.001) weight and volume of intestinal content. CONCLUSIONS: The remarkable anti-diarrheal effect of C.gigantea extract against castor oil-induced diarrhea model attests to its utility in a wide range of diarrheal states