Diabetes mellitus is one of the leading causes of morbidity and mortality globally. Although synthetic hypoglycemic agents are commonly used to manage this disorder, such medications, besides being unable to cure the disease, are expensive and associated with side effects. Conversely, medicinal plants have emerged as effective, safe and affordable alternative treatments. Boswellia dalzielii plant has been reported to possess ethnomedicinal properties for the treatment of various health conditions; however, scientific studies exploring this plant as antihyperglycemic agent are still limited. Thus, this study evaluated the antihyperglycemic activity of aqueous stem bark extract (ASBE) of B. dalzielii in alloxan-induced diabetic Wistar albino rats. Phytochemical screening of the ASBE of B. dalzielii was conducted. Twenty male Wistar albino rats weighing 100–150 g divided into 4 groups (A–D) of five rats were used for the study. Group A served as the normal control and received neither ASBE of B. dalzielii nor glibenclamide. The treatment for the other three groups was as follows: Group B, 10 mg/kg of glibenclamide (diabetic control); Group C, 500 mg/kg ASBE of B. dalzielii; and Group D, 1000 mg/kg ASBE of B. dalzielii. Treatments were administered orally every 24 h for a period of 2 weeks. Blood glucose level and body weight were evaluated at weeks 0, 1 and 2. Histomorphological features of the rats’ pancreas in all the groups were compared. The phytochemical analysis revealed the presence of alkaloids, saponins, tannins, cardiac glycosides, flavonoids, carbohydrates, steroids and triterpenes. The two different doses of the plant extract significantly reduced blood glucose level at weeks 1 and 2 (all p  中文翻译： 乳香树皮水提取物对四氧嘧啶诱导的糖尿病 Wistar 大鼠的降血糖活性评价 糖尿病是全球发病率和死亡率的主要原因之一。虽然合成降糖药通常用于治疗这种疾病，但此类药物除了无法治愈这种疾病外，还很昂贵并且有副作用。相反，药用植物已成为有效、安全和负担得起的替代疗法。据报道，乳香植物具有治疗各种健康状况的民族药用特性；然而，探索这种植物作为抗高血糖剂的科学研究仍然有限。因此，本研究评估了达氏双氧嘧啶水性茎皮提取物 (ASBE) 在四氧嘧啶诱导的糖尿病 Wistar 白化大鼠中的抗高血糖活性。对 B. dalzielii 的 ASBE 进行了植物化学筛选。将 20 只体重 100-150 g 的雄性 Wistar 白化大鼠分成 4 组（A-D），每组 5 只用于该研究。A 组作为正常对照，既不接受达氏双胞胎的 ASBE，也不接受格列本脲。其他三组的治疗如下：B组，10mg/kg格列本脲（糖尿病对照）；C 组，500 mg/kg ASBE 的 B. dalzielii；和 D 组，1000 mg/kg ASBE 的 B. dalzielii。每 24 小时口服一次治疗，持续 2 周。在第0、1和2周评估血糖水平和体重。比较各组大鼠胰腺的组织形态学特征。植物化学分析显示存在生物碱、皂苷、单宁、强心甙、类黄酮、碳水化合物、类固醇和三萜。两种不同剂量的植物提取物在第 1 周和第 2 周显着降低了血糖水平（所有 p < 0.05），与第 2 周的格列本脲相比，1000 mg/kg 剂量的降幅更大（p = 0.014）。然而，只有 500 mg/kg 的剂量导致胰岛细胞的恢复，尽管是轻微的。这项研究表明，达氏双歧杆菌植物表现出有效的抗高血糖活性，这可以通过降低血糖水平和胰岛细胞的轻微恢复来证明。因此，可以考虑将这种植物用于治疗糖尿病。的胰岛细胞。这项研究表明，达氏双歧杆菌植物表现出有效的抗高血糖活性，这可以通过降低血糖水平和胰岛细胞的轻微恢复来证明。因此，可以考虑将这种植物用于治疗糖尿病。的胰岛细胞。这项研究表明，达氏双歧杆菌植物表现出有效的抗高血糖活性，这可以通过降低血糖水平和胰岛细胞的轻微恢复来证明。因此，可以考虑将这种植物用于治疗糖尿病。

Curcumin is a bright colored polyphenolic moiety which is derived from the rhizomes of Curcuma longa of family Zingiberaceae. Its simple molecular structure, high efficacy, variable therapeutic effects and multidimensional use make it ideal for various treatment regimens. It has been used for centuries for its antioxidant, anti-inflammatory and antibacterial characteristics which makes it ideal in the determent and treatment of skin inflammation, psoriasis, acne, premature skin aging and skin cancers. It also exhibits antiviral, antiulcer, anticarcinogenic, antimutagenic, antibacterial, hypocholesteremia and antifungal, benefits making it a perfect multifunctional moiety for treating numerous disorders. Curcumin offers protection against skin damage induced by persistent UVB exposure. Curcumin has substantial therapeutic potentials against various skin conditions like anti-inflammatory, antioxidant effects, wound healing efficiency any many more. It illustrates a multiplicity of important medicinal properties which has a great potential in treating various dermatological diseases. The study seeks to provide a comprehensive update on curcumin and its exceptional medicinal profile, which can be efficaciously and appropriately utilized in treating skin conditions like psoriasis, acne, dermatitis, scleroderma, skin cancers, skin aging, fungal infections and wounds.

Luffa cylindrica (L.) is an annual climbing plant that produces fibrous fruit and can also be used as a vegetable in northern parts of India. Various studies have been carried out on the plant and found to have anti-inflammatory, antifungal, analgesic, anti-myocardial, anti-hyper triglyceride, immunostimulant, anti-allergic, and other properties. The ethanolic extract of the Luffa cylindrica (L.) fruit has not yet been subjected to LC–MS analysis for several bioactive chemicals that target neurological diseases. Oxidative stress is an inevitable situation in AD mechanisms and is a key bridge connecting various AD pathways. Luffa cylindrica contains various phytochemicals and showed highest alkaloid content of 21.39 ± 1.47 mg of AE/g. A total of 80 compounds were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for eligibility by Lipinski's rule of five for docking with receptors responsible for causing oxidative stress-associated Alzheimer's disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 µg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of − 46.1 kcal/mol showing promising drug for Alzheimer's disease. Based on current findings, the study reports the presence of a promising, bioactive compound (perlolyrine) and in turn provides an optimistic note in exploring its biological activity in vivo with oxidative stress-related Alzheimer's disease.

In diabetic animals, there is a significant increase in plasma glucose, serum total cholesterol, triglyceride, and low-density lipoprotein levels, and decreased body weight, liver and muscle glycogen, and high-density lipoprotein. Effective treatment of diabetes mellitus is not yet known, even though the management of diabetes mellitus is considered a global concern. Plants and herbs have played an important role in the healthcare of many societies throughout history. Today’s researchers are investigating the potential for using these nonpharmaceutical approaches to treat and control diabetes, either in conjunction with standard treatments or as an alternative to them. Herbal formulations are favored because to lower cost and fewer side effects compared to other methods for alleviating diabetes and its consequences. In ethnomedicinal practices, different parts of Mangifera indica are used to treatment of diabetes. The present investigation was undertaken to evaluate the antidiabetic activity of an ethanolic extract of Mangifera indica and mangiferin in alloxan-induced diabetic rats. This experiment was conducted in a set of two with four groups of animals namely control (Tc), treatment alloxan (Ta), treatment extract (Tae), and treatment mangiferin (Tam). To develop diabetes, Wistar rats treated with 150 mg/kg b.w. of alloxan monohydrate were injected intraperitoneally. Tae and Tam’s groups received a freshly prepared single dose of extract and mangiferin in distilled water via the oral route. All experimental groups received laboratory pallet feed diet and drinking water ad libitum. Diabetic rats were treated for 21 days with an ethanolic extract of mango peel and pure mangiferin orally daily at rates of 200 mg/kg b.w. and 20 mg/kg b.w. An alloxan-induced diabetic rat treated with mango peel extract and mangiferin significantly improved the overhead impact due to diabetes. There was a significant (p  中文翻译： 芒果皮提取物和芒果苷对四氧嘧啶诱导的糖尿病大鼠的抗糖尿病活性 在糖尿病动物中，血浆葡萄糖、血清总胆固醇、甘油三酯和低密度脂蛋白水平显着升高，体重、肝糖原和肌肉糖原以及高密度脂蛋白降低。糖尿病的有效治疗尚不清楚，尽管糖尿病的管理被认为是全球关注的问题。纵观历史，植物和草药在许多社会的医疗保健中发挥了重要作用。今天的研究人员正在研究使用这些非药物方法治疗和控制糖尿病的可能性，无论是与标准治疗相结合还是作为它们的替代方法。与其他减轻糖尿病及其后果的方法相比，草药配方成本更低、副作用更少，因此受到青睐。在民族医学实践中，芒果的不同部分用于治疗糖尿病。本研究旨在评估芒果乙醇提取物和芒果苷对四氧嘧啶诱导的糖尿病大鼠的抗糖尿病活性。该实验以两组动物为一组进行，有四组动物，即对照组 (Tc)、治疗四氧嘧啶 (Ta)、治疗提取物 (Tae) 和治疗芒果苷 (Tam)。为患上糖尿病，向 Wistar 大鼠腹腔注射 150 mg/kg bw 的四氧嘧啶一水合物。Tae 和 Tam 的小组通过口服途径接受新鲜配制的单剂量提取物和芒果苷蒸馏水。所有实验组都接受实验室托盘饲料饮食和随意饮用水。糖尿病大鼠每天口服 200 毫克/千克体重和 20 毫克/千克体重的芒果皮乙醇提取物和纯芒果苷，持续 21 天糖尿病的影响。四氧嘧啶诱导的糖尿病大鼠 (Ta) 体重显着下降 (p < 0.05)，而给予芒果皮提取物和芒果苷的动物在 2 周后与对照组相比体重显着增加。四氧嘧啶诱导的大鼠 (Ta) 组血糖水平较高，与对照组有显着差异 (p < 0.01)。与糖尿病动物相比，芒果皮提取物和芒果苷在治疗 21 天后显着降低了空腹血糖水平。芒果皮提取物和芒果苷通过增加肌肉和肝脏中的糖原水平来影响糖尿病组的糖原合成途径。与对照组相比，发现芒果皮提取物和芒果苷对血浆胆固醇和高密度脂蛋白水平没有显着影响。与对照组相比，芒果皮提取物的低密度脂蛋白水平有显着差异 (p < 0.05)。与对照组相比，芒果苷在甘油三酯和极低密度脂蛋白水平方面存在显着差异 (p < 0.05)。对四氧嘧啶引起的 I 型糖尿病大鼠的胰腺组织病理学检查发现，使用芒果皮乙醇提取物和芒果苷进行治疗可恢复 β 细胞功能以及朗格汉斯岛的再生。芒果皮提取物和芒果苷具有抗糖尿病、

Venous thromboembolism is one of the critical complications of bariatric surgeries resulting in life-threatening outcomes. The benefits and duration of appropriate thromboprophylaxis in the morbidly obese patients stay unclear. The study aims to compare the benefits of in-hospital thromboprophylaxis versus extended thromboprophylaxis post-bariatric surgery among a cohort with a high prevalence of morbid obesity. A retrospective observational cohort study was conducted on 229 morbidly obese patients who had undergone bariatric surgery in a tertiary care teaching hospital in Saudi Arabia. Upon discharge, the patients were split either to receive no thromboprophylaxis or enoxaparin 40 mg once or twice daily for 14–21 days post-discharge. Primary outcomes were the clinical difference between the study groups in the percentage of patients who developed a symptomatic venous thromboembolic event during postoperative hospitalization or after discharge. Among patients who received no thromboprophylaxis (n = 119), no one developed a venous thromboembolic event, while, in the extended prophylaxis group (n = 110), 1.82% developed a non-fatal one (P = 0.23). Additionally, no significant difference in percentages of bleeding events occurred in both groups (p = 0.054). The incidence of venous thromboembolism and bleeding events that occurred with extended thromboprophylaxis were deemed comparable and non-significant to the conventional in-hospital thromboprophylaxis. However, portal thrombosis stays an enigmatic complication despite its documented sparsity in literature.

The purpose of the current study was to examine the potential impact of a methanolic extract of Areca catechu nut (MAN) on handling-induced convulsions (HIC), anxiety and anhedonia behaviour of alcohol-withdrawn mice. 30 female Swiss albino mice were divided into 5 groups, each with 6 animals. Group 1 (saline withdrawal) received saline during the 3-day alcohol/saline induction phase, while the other 4 groups (alcohol withdrawal) received 20% v/v ethanol (1.25 ml/100 g body weight, i.p.; 20% v/v ethanol was made from absolute ethanol with 79.9 ml saline + 0.1 ml fomepizole, an alcohol dehydrogenase inhibitor). Day four (test day) involved studying handling-induced convulsions; open field test (OFT), elevated plus maze test (EPM), marble burying test (MBT) for anxiety; 24-h sucrose preference test (SPT) for anhedonia in mice. On the test day, Group I and II (saline withdrawal and alcohol withdrawal) received oral treatments with 1% w/v sodium carboxyl methylcellulose 1 h prior to the behavioural testing. Group III received an injection of diazepam (1 mg/kg, i.p., 30 min prior) and Group IV and V were treated with two different doses of MAN (50 and 100 mg/kg, p.o.) 1 h prior to the behavioural test. At doses of 50 and 100 mg/kg, p.o., the Areca catechu nut methanolic extract significantly reduced handling convulsions and anxiety, and had an anti-anhedonic effect using various evaluation criteria, such as convulsion score (HIC), no. of central and peripheral line crossings (OFT), % entries and time spent in open arms (EPM), no. of marbles buried (MBT), and sucrose intake ratio (SPT) in alcohol-withdrawn mice. In mice undergoing alcohol withdrawal, Areca catechu nut extract (MAN) greatly lessens handling-induced convulsions, anxiety and depression symptoms.

Nateglinide and metformin HCl are used in combination for the treatment of type 2 diabetes. A simple, sensitive and reliable UPLC method was developed for simultaneous estimation of nateglinide and metformin HCl using Phenomenox C18 (50*2.1 mm, 3.5 µm) column at ambient temperature as stationary phase in addition to mobile phase containing 75 volumes of ammonium formate buffer (pH = 3) along with 25 volumes of acetonitrile with a flow rate of 0.2 mL/min with UV detection at 260 nm and a run time of 3 min. The developed method was validated as per ICH Q2(R1) guidelines. The separation of metformin HCl and nateglinide was done at retention times of 1.014 min and 1.435 min, respectively. The mean % recovery for nateglinide and metformin HCl in the accuracy study was observed to be 99.9% and 99.2%, respectively. LOD and LOQ values were determined considering the S/N ratio and were found to be 0.09 µg/mL and 0.3 µg/mL, respectively, for nateglinide and 0.75 µg/mL and 2.5 µg/mL, respectively, for metformin HCl. The method was found to be precise with % RSD values of 0.58 and 0.45, respectively, for repeatability and intermediate precision of nateglinide and 0.43 and 0.43, respectively, for repeatability and intermediate precision of metformin HCl which were within acceptance criteria. The method was found to be linear in the range of 7.5–45 µg/mL and 62.5–375 μg/mL for nateglinide and metformin HCl, respectively. The regression equations for nateglinide and metformin HCl were found to be y = 17377x + 6543.4 and y = 18439x + 43,537, respectively. The method was found to be robust by deliberate changes in the method parameters like flow rate and mobile phase composition. Forced degradation studies were performed as per ICH Q1A(R2) and Q1B guidelines, and peak purity was observed in all types of degradation studies for both the drugs. The developed method was found to be satisfactory as it is simple, sensitive, accurate, precise, robust, rapid, economical and yet stability indicating and can be applied successfully in the routine laboratory analysis for the simultaneous estimation of nateglinide and metformin HCl in the bulk and pharmaceutical dosage forms.

The lactic acid bacteria (LAB), from diverse sources, are of great importance as probiotics, and several authors from around the globe have reported LAB, isolated from various fermented foods, as potential antimicrobial agents. The current study explored the antibacterial activity and probiotic property of idli batter isolates of LAB, for the first time from Malda (West Bengal, India). The LAB procured from fresh and fermented idli batter samples had antibacterial activity against pathogenic as well as food-borne bacteria with zone diameter of inhibition of 16, 18 and 23 mm with concentrations 25, 50 and 75 μl/well, respectively, as determined by agar-well diffusion method. The identification of isolated LAB was executed through biochemical tests, 16S rRNA gene sequencing and phylogenetic analysis. The LAB isolates from fresh idli batter: LMEM1001 and LMEM1002, showed maximum (96.81% and 95.20%, respectively) similarities with Lactiplantibacillus pentosus and Lactiplantibacillus plantarum, respectively, whereas the fermented idli batter isolates, LMEM1006 and LMEM1008, showed maximum (96.11% and 98.40%, respectively) similarities with Lactiplantibacillus plantarum and Limosilactobacillus fermentum, respectively. Safety profiling of isolated LAB was executed using antibiogram, DNase and gelatinase tests. The idli batter-derived lactobacilli have been demonstrated as good probiotics, which displayed excellent antibacterial activity against clinical and food-borne bacteria. Overall, the idli batter isolates of LAB might be useful as probiotics for human consumption and as biotherapeutics in combating bacterial antibiotic resistance.

Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a progressive neurodegenerative disorder that gradually affects cognitive function and eventually causes death. Most approved drugs can only treat the disease alleviating the disease symptoms; therefore, there is a need to develop drugs that can treat this illness holistically. The medical community is searching for new drugs and new drug targets to cure this disease. In this study, QSAR, molecular docking evaluation, and ADMET/pharmacokinetics assessment were used as modeling methods to identify the compounds with outstanding physicochemical properties. The 37 MAO-B compounds were screened using the aforementioned methods and yielded a model with the following molecular properties: AATS1v, AATS3v, GATS4m, and GATS6e. Good statistical values were R2train = 0.69, R2adj = 0.63, R2pred = 0.57, LOF = 0.23, and RMSE = 0.38. The model was validated using an evaluation set that confirmed its robustness. The molecular docking was also utilized using crystal structure of human monoamine oxidase B in complex with chlorophenylchromone-carboxamide with ID code of 6FW0, and three compounds were identified with outstanding high binding affinity (13 = − 30.51 kcal mol−1, 31 = − 31.85 kcal mol−1, and 33 = − 33.70 kcal mol−1), and better than the Eldepryl (referenced) drug (− 11.40 kcal mol−1). These three compounds (13, 31, and 33) were analyzed for ADMET/pharmacokinetics evaluation and found worthy of further analysis as promising drug candidates to cure AD and could also serve as a template to design several monoamine oxidase B inhibitors in the future to cure AD.

A precise, accurate, economical and reproducible UV, RP-HPLC and UPLC method has been developed for the estimation of Prenoxdiazine hydrochloride in pharmaceutical and bulk dosage form. Each of the developed method has been validated for the analysis of Prenoxdiazine hydrochloride. The validation of the analytical methods was carried out based on various parameters like precision, linearity, accuracy, specificity, LOD, and LOQ for all the three methods. The parameters were found statistically significant for the analysis of Prenoxdiazine hydrochloride. The method was found sensitive in the presence of analytical impurities. The retention time of the Prenoxdiazine HCl was found to be 2.5 and 2.9 min, using common solvents acetonitrile and methanol, in UPLC and HPLC, respectively. The method may be useful in the wide range of analysis for the estimation of Prenoxdiazine hydrochloride. It is found to be robust upon the change in solvent flow rate, column temperatures. Further, the study has investigated the stability of the sample under stressed condition like thermal, oxidative, and photolytic. Here, we tried to develop and compare cost-effective methods for Prenoxdiazine HCl using most common industrial methods which are never studied.

The popular Leucopaxillus gentianeus mushroom contains very high nutrients and bioactive compounds with good anti-breast cancer activity. The til oil extract seems to be the most active in preparation. This study aims to find the best extract using different solvents for extraction, to measure the total cucurbitacin content and anti-breast cancer activity in vitro of til oil extract of leucopaxillus gentianeus. The dry mushroom material was extracted using continuous hot extraction with til oil, petroleum ether, ethyl acetate, chloroform, methanol, and water of leucopaxillus gentianeus which were used for phytochemical analysis, HPLC method was used for no of phytochemical and anti-breast cancer activity in vitro. The total cucurbitacin content was found based on the HPTLC method. The anti-breast cancer activity was carried out using progesterone and estrogen activity. The number of pecks found during HPLC it is indicated that the list of phytochemical presents in a different extract, also good yield found with til oil extract was 6.8 gm. Progesterone and estrogen inhibited high with til oil extract and cucurbitacin content was found to be 264.00 ng. The significance of the biotherapeutic effects increases with the number of bioactive components in the preparation. Leucopaxillus gentianeus til oil extract has high cucurbitacin content and strong anti-breast cancer properties.

Myocardial infarction is a significant health issue in both wealthy and underdeveloped nations. Globally, it is the leading cause of deaths among cardiovascular diseases. In 2012, myocardial infarction-related deaths were about 14.1 million out of 17.5 million cardiovascular disease-related deaths. Clinical management of myocardial infarction remains a challenge because most conventional drugs provide symptomatic relief only. In addition, conventional remedies are associated with numerous advese effects and arguably, in many cases are quite expensive. Hence, herbal remedies, which are widely available, with comparatively fewer side effects, and are affordable, provide a more attractive therapeutic alternative. This study aimed at determining cardiopreventive effects of aqueous leaf extracts of X. americana and P. capensis. Phytochemical screening was done using liquid chromatography-mass spectrometry. Wistar albino rats were employed to test for cardiopreventive effects of the extracts and were randomized into 6 groups of 5 animals each. Groups I, II, and III were normal, negative, and positive controls, respectively, and rats were given normal saline, salbutamol (7.5 mg/Kg bw), and propranolol, respectively. Groups IV, V, and VI rats were treated with extracts dose levels 50, 100, and 150 mg/Kg bw, respectively. Biochemical analysis was done to determine effects of the extracts on levels of serum cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, and lipid profiles. Levels of oxidative stress markers were determined in the heart tissue. The LC–MS analysis revealed different phytocompounds in the extracts, including flavonoids, phenolic acids, glycosides and tannins, which are known to confer cardioprotective activities. The extracts significantly prevented increase in cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, total cholesterol, triglycerides, LDL, and MDA levels, as well as a significant increase in superoxide dismutase, catalase, glutathione peroxidase, and HDL levels. This study confirmed that Ximenia americana and Pappea capensis extracts have the potential to prevent myocardial infarction in rats. Generally, P. capensis extract showed better activity as compared to X. americana extract. The effects of the extracts could be attributable to the presence of various cardioactive phytocompounds. Therefore, these plants can be considered in the development of potent and safe cardiopreventive drugs.

Medicinal plant contains multiple bioactive compounds with therapeutic potentials. Due to their availability, affordability, and minimal known side effects, they are widely practiced. Identification, quantification, and establishment of their interaction with physiological enzymes help in the standardization of plant-based medicinal extracts. In this study, gas chromatography/flame ionization detector (GC–FID) and high-performance liquid chromatography (HPLC) analysis were used to determine the bioactive components in the ethanol extract of Newbouldia laevis stem bark. The antioxidant activity of the extract was determined. Enzyme inhibitory potency of the flavonoids’ components was investigated against acetylcholinesterase, butyrylcholinesterase, phospholipase A2, α-glucosidase, and α-amylase. Analysis of ethanol extract of N. laevis stem-bark revealed alkaloids (0.37%), tannins (1.82 mg/TEq/g), flavonoids (5.85 mg/QEq), steroids (0.11 mg/10 g) and glycosides (0.08 mg/10 g). The HPLC fingerprint of flavonoids showed high concentrations (mg/100 g) of catechin (47.11), apigenin (15.68), luteolin (18.90), kaempferol (41.54), and quercetin (37.64), respectively. In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability of the extract was exhibited at 150 and 200 mg/mL, respectively. At 300 mg, most in vitro antioxidant potentials (lipid peroxidation, metal chelating ability, hydroxyl, nitric oxide, sulfide oxide radicals scavenging abilities) were obtained. The extract showed varying inhibitory abilities (> 50%) on acetylcholinesterase, butyrylcholinesterase, phospholipase A2, α-glucosidase and α-amylase at 300 mg/mL, IC50 of 129.46, 237.10, 169.50, 251.04 and 243.06 mg/mL, respectively, with inhibition constants (Ki) of 3.92, 1.63, 1.11, 2.95 and 2.11. Results showed an affinity for the targeted enzymes with free energies higher than the standard drugs. The results revealed that the N. laevis stem bark possesses antioxidant activity and enzyme inhibitory activity on the physiological enzyme that has been implicated in diabetes. In vitro and in silico inhibition of these physiological enzymes by extract suggests that the stem bark can be effective in ameliorating the complications associated with diabetes mellitus.

Hemodynamic regulation is a substantial part of the physiological integrity of the human body. It is based on the delivery of proper blood perfusion to every organ. Five primary vasoactive substances are nearly located throughout the human body, either released from the endothelium, prostanoids, nitric oxide (NO), and endothelin-1 (ET-1); or considered as hormones, bradykinin (BK) and natriuretic peptides (NPs). The circulating mediators are in synchronization with the renin–angiotensin system (RAS) during the pathogenesis of the main vital organs, heart, kidney, lung, liver, and brain. The RAS system has been an extensive therapeutic approach for cardiovascular and renal diseases for decades, but more recently became a crucial regulator of hemodynamics in other organs after the actions of its components were detected in other organs. All the mentioned disorders here begin with the initiation of abnormal imbalance between vasoactive mediators which causes vascular dysfunction and histopathological situations that may induce oxidative stress which exaggerates the disorder if there is no clinical intervention. We will review the currently identified signaling pathways and the possible relationships between those compounds elucidating how they interfere with serious diseases including cardiovascular diseases (CVDs), chronic kidney disease (CKD), pulmonary arterial hypertension (PAH), portal hypertension (PHT), and Alzheimer's disease (AD). Thus, this updated review summarizes years of work that aims to define the contribution of each mediator in both normal and pathological states, besides the drugs based on their activity and their places in either preclinical or clinical trials.

Acne vulgaris is a very dangerous skin disease leads to psychological disorders. Benzoyl peroxide and tretinoin in combination with topical dosage are used to improve the appearance of acne-prone skin. The study aimed to develop and validate an HPLC–PDA method for the simultaneous estimation of both drugs. Intentional modifications were implemented in the analytical method to get better optimum conditions. The final method was chosen for the reverse phase chromatographic separation by using the C18 column as a stationary phase and 0.01 M phosphate buffer adjusted pH 2.5 mixed with acetonitrile (25:75 v/v) as a mobile phase. The optimized conditions were 1.5 mL/min flow rate, 30 °C column temperature, 5 °C autosampler temperature, and 20 µL injection volume. The wavelength was chosen for detection of Benzoyl peroxide at 272 nm and Tretinoin at 353 nm by utilizing a PDA detector. All standard and sample solutions were made in methanol. The developed method exhibited peak retention times of 2.94 min for Benzoyl peroxide and 11.34 min for Tretinoin. This analytical method was proven to be robust, linear in calibration curve, accurate, precise, and specific. The forced degradation studies results showed that a high degree of specificity was obtained by separating both analytes from produced impurities completely. The developed analytical method is fast, economic and stability indicating. It is useful for routine pharmaceutical analysis where the combination of benzoyl peroxide and tretinoin is formulated for their quality and safety.

Oxalis corniculata is a well-known medicinal plant used in folk medicine for the management of many diseases. The aim is to determine the physico-chemical properties, microscopic study, phytochemical properties, in-silico, in-vitro antioxidant and anticancer activity on human Hepatocarcinoma (Hep-G2) cell line of O. corniculata plant extract. Microscopical study reaveals that presence of pericyclic fibres, starch gains, trichomes etc, and phytochemical screening is carried to find out secondary metabolites. The molecular docking study concluded that some of the phytocompounds showed inhibition of epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) inhibitor. Furthermore, ADMET and drug likeness study hints some of phytocompounds may act as lead for anticancer drug discovery and development. Among selected phytocompounds, compound apigenin possesses − 7.90 kcal/mol as compared to standard drug doxorubicin possesses − 7.63 kcal/mol against the epidermal growth factor receptor tyrosine kinase. The plant extract shown antioxidant activities based on the different tests were performed. The hydroalcoholic plant extracts were found to be selectively cytotoxic in vitro to human Hepatocarcinoma (Hep-G2) cell line with IC50values 34.494 ± 0.42 µg/ml and EAF showed at IC50 value 30.245 ± 0.58 µg/ml of the cells were inhibited at the concentration of 50 µg/ml as compared with standard doxorubicin at IC50 value 24.8939 ± 0.25 µg/ml, respectively. The present study concluded that O. corniculata possesses potential antioxidant and cytotoxic properties based upon the computer aided drug design models and in-vitro activity.

The class of heterocyclic compounds exhibits a variety of pharmacological actions, long employed as an active ingredient in drug design and production. Indole and its derivatives are crucial in medicinal chemistry. Due to its physiological action, it has been gaining a lot of interest by exhibiting antibacterial, anticonvulsant, antifungal, antimalarial, antidiabetic, antidepressant, anticancer, and antimicrobial properties. The indole moiety constitutes a benzene ring fused with a pyrrole ring to form a bicyclic structure with a nitrogen atom as the major component and is produced by a variety of techniques. The sulfonamide analogs of indole usually referred to as sulfa medicines have recently been produced and exhibit strong antimicrobial actions. The goal of this work is to present the most recent methods for synthesizing indole-sulfonamide derivatives, together with data on their reported activities and synthetic scheme from 2010 to 2023. We anticipate that this review will help medicinal chemists rationally develop pharmacologically active derivatives of indole with sulfonamide scaffolds.

NOX-1 overexpression has been observed in various studies, persons with diabetes or cardiovascular conditions. NOX-1 orchestrates the disease pathogenesis of various cardiovascular conditions such as atherosclerotic plaque development and is a very crucial biomarker. Therefore, this study was carried out to deduce the three-dimensional modelled structure of NOX-1 using DeepMind AlphaFold-2 to find meaningful insight into the structural biology. Extensive in silico approaches have been used to determine the active pocket, virtually screen large chemical space to identify potential inhibitors. The role of the key amino acid residues was also deduced using alanine scanning mutagenesis contributing to the catalytic process and to the overall stability of NOX-1. The modelled structure of NOX-1 protein was validated using ERRAT. The ERRAT statistics with 9 amino acids sliding window have shown a confidence score of 96.937%. According to the Ramachandran statistics, 96.60% of the residues lie within the most favoured region, and 2.80% of residues lie in the additionally allowed region, which gives an overall of 99.4% residues in the three quadrants in the plot. GKT-831 which is a referral drug in this study has shown a GOLD interaction score of 62.12 with respect to the lead molecule zinc000059139266 which has shown a higher GOLD score of 78.07. Alanine scanning mutagenesis studies has shown that Phe201, Leu98 and Leu76 are found to be the key interacting residues in hydrophobic interactions. Similarly, Tyr324, Arg287 and Cys73 are major amino acid residues in the hydrogen bond interactions. NOX-1 overexpression leads to heightened ROS production resulting in catastrophic outcomes. The modelled structure of NOX-1 has a good stereochemistry with respect to Ramachandran plot. The lead molecule zinc000059139266 has shown to have a very high interaction score of 78.07 compared to the referral drug GKT-831 with a score of 62.12. There is an excellent scope for the lead molecule to progress further into in vitro and in vivo studies.

Drug metabolism is crucial to attaining the therapeutic index of any drug. The metabolism and elimination of the drugs are governed mainly by P-glycoprotein (P-gp) and Cytochrome P450 (CYP). Paracetamol is mostly used as analgesic and antipyretic agent. The metabolism of paracetamol is primarily via Glucuronidation and sulphation at therapeutic doses. About 5–10% of paracetamol is metabolized via CYP mediated pathway. Cytochrome P450 2E1 (CYP2E1) is primarily responsible for forming a toxic metabolite of paracetamol called N-acetyl-p-benzoquinoneimine (NAPQI). Even at therapeutic doses, long-term usage of paracetamol leads to the hepatic and nephrotoxicity because of NAPQI. Several in-vitro and in-vivo studies conducted by different research groups and reported that chlorzoxazone is a substrate and inhibitor of CYP2E1. However, the effect of chlorzoxazone on the paracetamol (CYP2E1 substrate) metabolism via the CYP2E1 has not yet been reported. This study investigated the effect of chlorzoxazone on the CYP2E1-mediated metabolism of Paracetamol and NAPQI formation in Wistar rats. For 15 days, animals were orally administered with Paracetamol (300 mg/kg) with and without Silymarin (100 mg/kg) (standard CYP2E1 inhibitor) and Chlorzoxazone (50 and 100 mg/kg). Analysis was performed using RP-HPLC on the 15th day to determine paracetamol and NAPQI concentration in the plasma. Paracetamol combination with chlorzoxazone (50 and 100 mg/kg) showed a dose-dependent increase in the AUC0–∞ and the peak plasma concentration (Cmax) of Paracetamol and a dose-dependent decrease of AUC0–∞ and Cmax of NAPQI compared to paracetamol control (p  中文翻译： 氯唑沙宗通过竞争性抑制 CYP2E1 介导的代谢来降低对乙酰氨基酚诱导的毒性 药物代谢对于达到任何药物的治疗指数至关重要。药物的代谢和消除主要受 P-糖蛋白 (P-gp) 和细胞色素 P450 (CYP) 控制。扑热息痛主要用作镇痛剂和解热剂。对乙酰氨基酚的代谢主要是通过治疗剂量的葡糖醛酸化和硫酸化。大约 5–10% 的对乙酰氨基酚通过 CYP 介导的途径代谢。细胞色素 P450 2E1 (CYP2E1) 主要负责形成一种名为 N-乙酰基-对苯醌亚胺 (NAPQI) 的对乙酰氨基酚有毒代谢物。即使在治疗剂量下，由于 NAPQI，长期使用扑热息痛也会导致肝和肾毒性。不同研究小组进行的几项体外和体内研究报告称氯唑沙宗是 CYP2E1 的底物和抑制剂。然而，氯唑沙宗通过 CYP2E1 对扑热息痛（CYP2E1 底物）代谢的影响尚未见报道。本研究调查了氯唑沙宗对 CYP2E1 介导的扑热息痛代谢和 Wistar 大鼠 NAPQI 形成的影响。连续 15 天，给动物口服扑热息痛 (300 mg/kg)，有和没有水飞蓟素 (100 mg/kg)（标准 CYP2E1 抑制剂）和氯唑沙宗（50 和 100 mg/kg）。在第 15 天使用 RP-HPLC 进行分析以确定血浆中扑热息痛和 NAPQI 的浓度。与扑热息痛相比，扑热息痛与氯唑沙宗（50 和 100 mg/kg）的组合显示扑热息痛的 AUC0–∞ 和峰值血浆浓度 (Cmax) 呈剂量依赖性增加，NAPQI 的 AUC0–∞ 和 Cmax 呈剂量依赖性降低控制（p < 0.001）。与扑热息痛对照相比，氯唑沙宗显着降低升高的肝脏和肾脏标志物。同时，肝脏和肾病组织研究表明，与扑热息痛对照组相比，氯唑沙宗的组合显着改善了扑热息痛引起的肝毒性和肾毒性。最后，这项研究表明，扑热息痛与氯唑沙宗联合使用可显着降低 NAPQI 的血浆水平，并通过抑制 CYP2E1 介导的代谢增强大鼠对扑热息痛的吸收。此外，氯唑沙宗显着改善扑热息痛引起的肝毒性和肾毒性。氯唑沙宗的组合显着改善了扑热息痛引起的肝毒性和肾毒性。最后，这项研究表明，扑热息痛与氯唑沙宗联合使用可显着降低 NAPQI 的血浆水平，并通过抑制 CYP2E1 介导的代谢增强大鼠对扑热息痛的吸收。此外，氯唑沙宗显着改善扑热息痛引起的肝毒性和肾毒性。氯唑沙宗的组合显着改善了扑热息痛引起的肝毒性和肾毒性。最后，这项研究表明，扑热息痛与氯唑沙宗联合使用可显着降低 NAPQI 的血浆水平，并通过抑制 CYP2E1 介导的代谢增强大鼠对扑热息痛的吸收。此外，氯唑沙宗显着改善扑热息痛引起的肝毒性和肾毒性。

Humans have used plants as a safe and effective medicine for a wide range of ailments ever since the earliest days of civilization. Calotropis procera potential as a treatment for a variety of ailments has been known for quite some time. This xerophytic, upright shrub grows to a height of about 6 m and can be found in the tropics of Africa and Asia. Its parts have been used to cure a variety of ailments, including rheumatism, fever, dysentery, diabetes, malaria, asthma, and many more. Here, we provide a synopsis of the available biological data and discuss the possible ways in which Calotropis procera could be used as a novel platform for the treatment of a wide range of diseases. High antioxidant, antiinflammatory, antianalgesic, antimicrobial, antimalaria, antidiabetic, wound-healing, hepato-protective, nerve-recovery, antiulcer, insecticidal, and anticancer effects have been observed in the latex. The research also found that excessive intake has negative health effects. The review discovered that the biological evaluation of C. procera in vitro and in vivo animal models was well documented. Human safety and efficacy, however, have yet to be thoroughly tested, and additional well-designed clinical trials are required to confirm preclinical findings. It is essential to establish a standard dose and assure its safety.