Current Pharmaceutical Design - Online First

Rumex nervosus Vahl is a phenomenal plant from Arabian Peninsula and East African areas. It potentially contains massive therapeutic phytochemicals, including Omeprazole, sitosterols, fatty acids, flavonoids and carotenes. Omeprazole (a commercial drug) is used to treat stomach ulcers, gastroesophageal reflux and cardiac disorders. Beta-sitosterol (commercial drug) reduces cholesterol levels and body swelling. It is also known to manage rheumatoid arthritis.

The present study evaluated the pharmacological potential and metabolite profiling of Rumex nervosus through various extracts. The extraction was performed using different solvents (Petroleum ether, Chloroform, n-Hexane, Butanol, Methanol, and distilled water) through soxhlet extraction method. Serial dilutions of (100-3.125 mg/mL) were prepared. The biological activities, antimicrobial, anti-diabetic, Hemolytic, anti-inflammatory, and antioxidant (DPPH radical Scavenging, Total anti-oxidant and total phenolic content assays) were performed. Statistical analysis of experimental data was carried out by using SPSS Version 20 and Origin 6.0. Data was represented as mean ± standard deviation (n=3). Differences among mean values were determined using Two-way ANOVA and Tukey’s test. The level of statistical significance was set at p ≤ 0.05. The potential extracts were further analyzed for phytochemicals through GC-MS and Network pharmacology (In silico approach).

The plant exhibited the best antioxidant activity (86.7% ± 1.92) at 100 mg/mL with distilled water extract. The highest anti-inflammatory activity (90.64 ± 2.34) (88.31 ± 2.37) was given by n-butanol and distilled water extracts at 100 mg/mL. The optimum anti-diabetic activity (92.78 ± 1.89) was observed at 100 mg/mL with n-butanol.

The maximum zone of inhibition was measured with n-butanol extract against Pseudomonas aeruginosa (36.67 ± 0.32) at 100 mg/mL, and in the case of Xanthomonas oryzae again n-butanol extract showed maximum zone of inhibition (30.47 ± 0.32) at 100 mg/mL. The maximum fungal zone of inhibition (22.33 ± 0.40) was noticed with n-butanol extract against Fusarium oxysporom at 100 mg/mL, and in the case of Aspergillus niger maximum fungal zone of inhibition was measured with n-butanol extract (16.20 ± 0.25) at 100 mg/mL. Hemolysis activity was highest (4.12 ± 0.01) with the methanol extract at 3.125 mg/mL. R. nervosus displayed the best activities with n-butanol and distilled water extract. GCMS and network pharmacology combined approach identified seven phytochemicals associated with oxidative stress and infectious diseases (1-Tetradecanol, Stigmast-5-ene, Phthalic acid 2-ethylhexyl isohexyl ester, A-Norcholestan-3-one, 5-ethenyl-, (5.beta.), 16-Heptadecenal, gamma-Sitosterol, Omeprazole). Degree score method selected 10 top hub genes, including AKT1, TNF, and EGFR, as potential targets for the identified phytochemicals. Omeprazole and 1-Tetradecanol are currently being used as medicines for treating gastric problems and inflammation.

R. nervosus has been confirmed as a potential source of these compounds through a multifaceted approach, hence it could thus be considered a safe, significant therapeutic source.

Osteoporosis (OP) is a prevalent condition in postmenopausal women, marked by reduced bone density and an increased risk of fractures. Raloxifene (RLX), a selective estrogen receptor modulator (SERM), is the only drug approved for the management of OP in this patient population. RLX works by mimicking estrogen's effects on bone, reducing bone resorption and thereby increasing bone mineral density. However, despite its benefits, conventional oral RLX formulations have significant limitations. Its low bioavailability and poor aqueous solubility are compounded by extensive first-pass metabolism, which significantly reduces the drug's efficacy. Recent research has focused on nanocarriers for RLX to overcome these challenges, with lipid-based nanocarriers emerging as a promising approach to improve solubility, enhance absorption, and bypass first-pass metabolism via lymphatic uptake.

The authors gathered information about RLX from articles published up to 2025 and listed in PubMed, Web of Science, Elsevier, Google Scholar, and similar databases. The keywords used in our search included “Osteoporosis” “Raloxifene” “nanocarriers” etc.

The review of existing literature reveals substantial progress in developing innovative drug delivery systems for RLX, aimed at overcoming the limitations of conventional oral dosage forms in the treatment of OP and cancer. Several studies underscore the potential of novel formulations, including lipid-based nanocarriers, to improve raloxifene's pharmacokinetic profile, particularly through enhanced solubility, dissolution rate, and bioavailability.

The nanocarriers mediated raloxifene delivery represent promising strategies to enhance its bioavailability and therapeutic efficacy in osteoporosis treatment. By improving solubility and bypassing first-pass metabolism, these novel systems can potentially reduce dose-related side effects, offering safer and more effective long-term options for postmenopausal women with osteoporosis. This approach supports the continued exploration of both oral and non-oral delivery methods to overcome the limitations of conventional raloxifene formulations.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity.

The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria.

They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties.

The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties.

GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features.

Endometriosis is a widespread estrogen-driven condition causing pelvic pain and infertility in women. This disease shares five features with cancer: Intrinsic growth signals, insensitivity to anti-proliferative signals, impaired apoptosis, induction of angiogenesis, and heightened tissue invasion, suggesting common therapeutic targets for both conditions. This article reviews studies investigating the anti-cancer drugs' protective effects and mechanisms in endometriosis treatment, providing essential insights into their efficacy and the relevant pathways in managing the disease.

A comprehensive review was conducted to assess the potential therapeutic benefits of anti-cancer drugs in endometriosis treatment. This included an extensive search of Google Scholar and PubMed, using relevant keywords without any limitations untilthe end of 2024, to ensure a thorough analysis of existing research in this field.

Many drugs used in treating estrogen-dependent and other cancers have demonstrated significant therapeutic potential for endometriosis, as supported by cellular, animal, and clinical studies.

Though these drugs may have significant side effects, more research is necessary to determine their usefulness in endometriosis treatment. By studying various drug dosages and regimens, researchers can aim to achieve effective treatment with minimal side effects. Personalized treatment based on illness severity can be achieved by selecting the right medication and dosage.

Future research can include optimizing dosages in preclinical studies, comparing repurposed drugs to conventional therapies in randomized trials, and conducting longer and larger clinical trials further to assess side effects and effectiveness in endometriosis patients.