Green Seaweed Caulerpa racemosa as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.

The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is Caulerpa racemosa, a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed C. racemosa were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in C. racemosa extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).

Mechanism of Action of Isoflavone Derived from Soy-Based Tempeh as an Antioxidant and Breast Cancer Inhibitor via Potential Upregulation of miR-7-5p: A Multimodal Analysis Integrating Pharmacoinformatics and Cellular Studies.

Breast cancer presents a significant global health challenge with rising incidence rates worldwide. Despite current efforts, it remains inadequately controlled. Functional foods, notably tempeh, have emerged as promising candidates for breast cancer prevention and treatment due to bioactive peptides and isoflavones exhibiting potential anticancer properties by serving as antioxidants, inducing apoptosis, and inhibiting cancer cell proliferation. This study integrates pharmacoinformatics and cellular investigations (i.e., a multifaceted approach) to elucidate the antioxidative and anti-breast cancer properties of tempeh-derived isoflavones. Methodologies encompass metabolomic profiling, in silico analysis, antioxidant assays, and in vitro experiments. Daidzein and genistein exhibited potential therapeutic options for breast cancer treatment and as antioxidant agents. In vitro studies also supported their efficacy against breast cancer and their ability to scavenge radicals, particularly in soy-based tempeh powder (SBT-P) and its isoflavone derivatives. Results have demonstrated a significant downregulation of breast cancer signaling proteins and increased expression of miR-7-5p, a microRNA with tumor-suppressive properties. Notably, the LD50 values of SBT-P and its derivatives on normal breast cell lines indicate their potential safety, with minimal cytotoxic effects on MCF-10A cells compared to control groups. The study underscores the favorable potential of SBT-P as a safe therapeutic option for breast cancer treatment, warranting further clinical exploration.

Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications.

Respiratory diseases are the most common and severe health complication and a leading cause of death worldwide. Despite breakthroughs in diagnosis and treatment, few safe and effective therapeutics have been reported. Phytochemicals are gaining popularity due to their beneficial effects and low toxicity. Polyphenols are secondary metabolites with high molecular weights found at high levels in natural food sources such as fruits, vegetables, grains, and citrus seeds. Over recent decades, polyphenols and their beneficial effects on human health have been the subject of intense research, with notable successes in preventing major chronic non-communicable diseases. Many respiratory syndromes can be treated effectively with polyphenolic supplements, including acute lung damage, pulmonary fibrosis, asthma, pulmonary hypertension, and lung cancer. This review summarizes the role of polyphenols in respiratory conditions with sufficient experimental data, highlights polyphenols with beneficial effects for each, and identifies those with therapeutic potential and their underlying mechanisms. Moreover, clinical studies and future research opportunities in this area are discussed.

Exploring Importance and Regulation of Autophagy in Cancer Stem Cells and Stem Cell-Based Therapies.

Autophagy is a globally conserved cellular activity that plays a critical role in maintaining cellular homeostasis through the breakdown and recycling of cellular constituents. In recent years, there has been much emphasis given to its complex role in cancer stem cells (CSCs) and stem cell treatment. This study examines the molecular processes that support autophagy and how it is regulated in the context of CSCs and stem cell treatment. Although autophagy plays a dual role in the management of CSCs, affecting their removal as well as their maintenance, the intricate interaction between the several signaling channels that control cellular survival and death as part of the molecular mechanism of autophagy has not been well elucidated. Given that CSCs have a role in the development, progression, and resistance to treatment of tumors, it is imperative to comprehend their biological activities. CSCs are important for cancer biology because they also show a tissue regeneration model that helps with organoid regeneration. In other words, the manipulation of autophagy is a viable therapeutic approach in the treatment of cancer and stem cell therapy. Both synthetic and natural substances that target autophagy pathways have demonstrated promise in improving stem cell-based therapies and eliminating CSCs. Nevertheless, there are difficulties associated with the limitations of autophagy in CSC regulation, including resistance mechanisms and off-target effects. Thus, the regulation of autophagy offers a versatile strategy for focusing on CSCs and enhancing the results of stem cell therapy. Therefore, understanding the complex interactions between autophagy and CSC biology would be essential for creating therapeutic treatments that work in both regenerative medicine and cancer treatment.

Revealing the mechanism and efficacy of natural products on treating the asthma: Current insights from traditional medicine to modern drug discovery.

Asthma remains a significant global health challenge, demanding innovative approaches to treatment. Traditional medicine has a rich history of using natural products to alleviate asthmatic symptoms. However, transitioning from these traditional remedies to modern drug discovery approaches has provided fresh insights into the mechanisms and effectiveness of these natural products. This study provides our comprehensive review, which examines the current state of knowledge in the treatment of asthma. It delves into the mechanisms through which natural products ameliorate asthma symptoms, and it discusses their potential in the development of novel therapeutic interventions. Our analysis reveals that natural products, traditionally employed for asthma relief, exhibit diverse mechanisms of action. These include anti-inflammatory, bronchodilatory, immunomodulatory effects, and reducing gene expression. In the context of modern drug discovery, these natural compounds serve as valuable candidates for the development of novel asthma therapies. The transition from traditional remedies to modern drug discovery represents a promising avenue for asthma treatment. Our review highlights the substantial efficacy of natural products in managing asthma symptoms, underpinned by well-defined mechanisms of action. By bridging the gap between traditional and contemporary approaches, we contribute to the growing body of knowledge in the field, emphasizing the potential of natural products in shaping the future of asthma therapy.

Unlocking the potential of flavonoids: Natural solutions in the fight against colon cancer.

Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, underscoring the importance of understanding the diverse molecular and genetic underpinnings of CRC to improve its diagnosis, prognosis, and treatment. This review delves into the adenoma-carcinoma-metastasis model, emphasizing the "APC-KRAS-TP53" signature events in CRC development. CRC is categorized into four consensus molecular subtypes, each characterized by unique genetic alterations and responses to therapy, illustrating its complexity and heterogeneity. Furthermore, we explore the role of chronic inflammation and the gut microbiome in CRC progression, emphasizing the potential of targeting these factors for prevention and treatment. This review discusses the impact of dietary carcinogens and lifestyle factors and the critical role of early detection in improving outcomes, and also examines conventional chemotherapy options for CRC and associated challenges. There is significant focus on the therapeutic potential of flavonoids for CRC management, discussing various types of flavonoids, their sources, and mechanisms of action, including their antioxidant properties, modulation of cell signaling pathways, and effects on cell cycle and apoptosis. This article presents evidence of the synergistic effects of flavonoids with conventional cancer therapies and their role in modulating the gut microbiome and immune response, thereby offering new avenues for CRC treatment. We conclude by emphasizing the importance of a multidisciplinary approach to CRC research and treatment, incorporating insights from genetic, molecular, and lifestyle factors. Further research is needed on the preventive and therapeutic potential of natural compounds, such as flavonoids, in CRC, underscoring the need for personalized and targeted treatment strategies.

Novel Functional Food Properties of Forest Onion (Eleutherine bulbosa Merr.) Phytochemicals for Treating Metabolic Syndrome: New Insights from a Combined Computational and In Vitro Approach.

Metabolic syndrome is a global health problem. The use of functional foods as dietary components has been increasing. One food of interest is forest onion extract (FOE). This study aimed to investigate the effect of FOE on lipid and glucose metabolism in silico and in vitro using the 3T3-L1 mouse cell line. This was a comprehensive study that used a multi-modal computational network pharmacology analysis and molecular docking in silico and 3T3-L1 mouse cells in vitro. The phytochemical components of FOE were analyzed using untargeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Next, an in silico analysis was performed to determine FOE's bioactive compounds, and a toxicity analysis, protein target identification, network pharmacology, and molecular docking were carried out. FOE's effect on pancreatic lipase, α-glucosidase, and α-amylase inhibition was determined. Finally, we determined its effect on lipid accumulation and MAPK8, PPARG, HMGCR, CPT-1, and GLP1 expression in the preadipocyte 3T3-L1 mouse cell line. We showed that the potential metabolites targeted glucose and lipid metabolism in silico and that FOE inhibited pancreatic lipase levels, α-glucosidase, and α-amylase in vitro. Furthermore, FOE significantly (p < 0.05) inhibits targeted protein expressions of MAPK8, PPARG, HMGCR, CPT-1, and GLP-1 in vitro in 3T3-L1 mouse cells in a dose-dependent manner. FOE contains several metabolites that reduce pancreatic lipase levels, α-glucosidase, α-amylase, and targeted proteins associated with lipid and glucose metabolism in vitro.

Current insights and future perspectives of flavonoids: A promising antihypertensive approach.

Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L-NG-nitro arginine methyl ester (L-NAME), an analog of L-arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L-NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L-NAME-induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L-NAME-induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin-converting enzyme (ACE) and endothelin-1. Moreover, they exhibit anti-inflammatory effects, attenuating inflammation-mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L-NAME-induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.

Antioxidants activities of phytochemicals perspective modulation of autophagy and apoptosis to treating cancer.

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.

Emerging trends of phytochemicals as ferroptosis modulators in cancer therapy.

Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.

Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.

Revealing Novel Source of Breast Cancer Inhibitors from Seagrass Enhalus acoroides: In Silico and In Vitro Studies.

Enhalus arcoides is a highly beneficial type of seagrass. Prior studies have presented proof of the bioactivity of E. acoroides, suggesting its potential to combat cancer. Therefore, this study aims to delve deeper into E. acoroides bioactive molecule profiles and their direct biological anticancer activities potentials through the combination of in-silico and in-vitro studies. This study conducted metabolite profile analysis on E. acoroides utilizing HPLC-ESI-HRMS/MS analysis. Two extraction techniques, ethanol and hexane, were employed for the extraction process. Furthermore, the in-silico study was conducted using molecular docking simulations on the HER2, EGFR tyrosine kinase and HIF-1α protein receptor. Afterward, the antioxidant activity of E. acoroides metabolites was examined to ABTS, and the antiproliferative activity was tested using an MTT assay. An in-silico study revealed its ability to combat breast cancer by inhibiting the HER2/EGFR/HIF-1α pathway through molecular docking. In addition, the MTT assay demonstrated that higher dosages of metabolites from E. acoroides increased the effectiveness of toxicity against cancer cell lines. Additionally, the study demonstrated that the metabolites possess the ability to function as potent antioxidants, effectively inhibiting a series of carcinogenic mechanisms. Ultimately, this study showed a new approach to unveiling the E. acoroides metabolites' anticancer activity through inhibiting HER2/EGFR/HIF-1α receptors, with great cytotoxicity and a potent antioxidant property to prevent a carcinogenic cascade.

Unraveling Light-Activated Insulin Action in Regulating Blood Glucose: New Photoactivatable Insight as a Novel Modality in Diabetes Management.

Diabetes, particularly type 2 diabetes (T2D), is the main component of metabolic syndrome. It is highly prevalent and has drastically increased with sedentary lifestyles, notably behaviors linked to ease of access and minimal physical activity. Central to this condition is insulin, which plays a pivotal role in regulating glucose levels in the body by aiding glucose uptake and storage in cells, and what happens to diabetes? In diabetes, there is a disruption and malfunction in insulin regulation. Despite numerous efforts, effectively addressing diabetes remains a challenge. This article explores the potential of photoactivatable drugs in diabetes treatment, with a focus on light-activated insulin. We discuss its advantages and significant implications. This article is expected to enrich the existing literature substantially, offering a comprehensive analysis of potential strategies for improving diabetes management. With its minimal physical intrusion, light-activated insulin promises to improve patient comfort and treatment adherence. It offers precise regulation and localized impact, potentially mitigating the risks associated with conventional diabetes treatments. Additionally, light-activated insulin is capable of explicitly targeting RNA and epigenetic factors. This innovative approach may pave the way for more personalized and effective diabetes treatments, addressing not only the symptoms but also the underlying biological causes of the disease. The advancement of light-activated insulin could revolutionize diabetes management. This study represents a pioneering introduction to this novel modality for diabetes management.

Inhibition of glycolysis and SIRT1/GLUT1 signaling ameliorates the apoptotic effect of Leptosidin in prostate cancer cells.

Since the silent information regulation 2 homolog-1 (sirtuin, SIRT1) and glucose transporter 1 (GLUT1) are known to modulate cancer cell metabolism and proliferation, the role of SIRT1/GLUT1 signaling was investigated in the apoptotic effect of Leptosidin from Coreopsis grandiflora in DU145 and PC3 human prostate cancer (PCa) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis, Western blotting, cBioportal correlation analysis, and co-immunoprecipitation were used in this work. Leptosidin showed cytotoxicity, augmented sub-G1 population, and abrogated the expression of pro-poly (ADP-ribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (pro-caspase3) in DU145 and PC3 cells. Also, Leptosidin inhibited the expression of SIRT1, GLUT1, pyruvate kinase isozymes M2 (PKM2), Hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA) in DU145 and PC3 cells along with disrupted binding of SIRT1 and GLUT1. Consistently, Leptosidin curtailed lactate, glucose, and ATP in DU145 and PC3 cells. Furthermore, SIRT1 depletion enhanced the decrease of GLUT1, LDHA, and pro-Cas3 by Leptosidin in treated DU145 cells, while pyruvate suppressed the ability of Leptosidin in DU145 cells. These findings suggest that Leptosidin induces apoptosis via inhibition of glycolysis and SIRT1/GLUT1 signaling axis in PCa cells.

Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo.

Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of Tapirira guianensis and its antitumor potential (in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 µg/mL, 83.07 µg/mL, 59.27 µg/mL and U251 with IC50 25.92 µg/mL, 37.3 µg/mL and 18.84 µg/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 - 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 - 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo. The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation.

The microRNA-193a-5p induced ROS production and disturbed colocalization between STAT3 and androgen receptor play critical roles in cornin induced apoptosis.

Though cornin is known to induce angiogenic, cardioprotective, and apoptotic effects, the apoptotic mechanism of this iridoid monoglucoside is not fully understood in prostate cancer cells to date. To elucidate the antitumor mechanism of cornin, cytotoxicity assay, cell cycle analysis, Western blotting, RT-qPCR, RNA interference, immunofluorescence, immunoprecipitation, reactive oxygen species (ROS) measurement, and inhibitor assay were applied in this work. Cornin exerted cytotoxicity, increased sub-G1 population, and cleaved PARP and caspase3 in LNCaP cells more than in DU145 cells. Consistently, cornin suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3) and disrupted the colocalization of STAT3 and androgen receptor (AR) in LNCaP and DU145 cells, along with suppression of AR, prostate-specific antigen (PSA), and 5α-reductase in LNCaP cells. Furthermore, cornin increased ROS production and the level of miR-193a-5p, while ROS inhibitor N-acetylcysteine disturbed the ability of cornin to attenuate the expression of AR, p-STAT3, PSA, pro-PARP, and pro-caspase3 in LNCaP cells. Notably, miR-193a-5p mimics the enhanced apoptotic effect of cornin, while miR-193a-5p inhibitor reverses the ability of cornin to abrogate AR, PSA, and STAT3 in LNCaP cells. Our findings suggest that ROS production and the disturbed crosstalk between STAT3 and AR by microRNA-193a-5p are critically involved in the apoptotic effect of cornin in prostate cancer cells.

Biochemical and molecular docking-based strategies of Acalypha indica and Boerhavia diffusa extract by targeting bacterial strains and cancer proteins.

Antibiotic-resistant microbes have emerged around the world, presenting a risk to health. Plant-derived drugs have become a potential source for the production of antibiotic-resistant drugs and cancer therapies. In this study, we investigated the antibacterial, cytotoxic and antioxidant properties of Acalypha indica and Boerhavia diffusa, and conducted in silico molecular docking experiments against EGFR and VEGFR-2 proteins. The metabolic extract of A. indica inhibited Streptococcus iniae and Staphylococcus sciuri with inhibition zones of 21.66 ± 0.57 mm and 20.33 ± 0.57 mm, respectively. The B. diffusa leaf extract produced inhibition zones of 20.3333 ± 0.5773 mm and 20.33 ± 0.57 mm against Streptococcus iniae and Edwardsiella anguillarum, respectively. A. indica and B. diffusa extracts had toxicities of 162.01 µg/ml and 175.6 µg/ml, respectively. Moreover, B. diffusa (IC50 =154.42 µg/ml) leaf extract exhibited moderately higher antioxidant activity compared with the A. indica (IC50 = 218.97 µg/ml) leaf extract. Multiple interactions were observed at Leu694, Met769 and Leu820 sites for EGFR and at Asp1046 and Cys1045 sites for VEGFR during the molecular docking study. CID-235030, CID-70825 and CID-156619353 had binding energies of -7.6 kJ/mol, -7.5 kJ/mol and -7.6 kJ/mol, respectively, with EGFR protein. VEGFR-2 protein had docking energies of -7.5 kJ/mol, -7.6 kJ/mol and -7.3 kJ/mol, respectively, for CID-6420353, CID-156619353 and CID-70825 compounds. The MD simulation trajectories revealed the hit compound; CID-235030 and EGFR complex, CID-6420353 and VEGFR-2 exhibit stable profile in the root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bond and root mean square fluctuation (RMSF) and the binding free energy by MM-PBSA method. This study indicates that methanol extracts of A. indica and B. diffusa may play a crucial role in developing antibiotic-resistant and cancer drugs.Communicated by Ramaswamy H. Sarma.

Effects of natural products on polycystic ovary syndrome: From traditional medicine to modern drug discovery.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with a worldwide prevalence of 6-10 % of women of reproductive age. PCOS is a risk factor for cardiometabolic disorders such as type 2 diabetes, myocardial infarction, and stroke in addition to exhibiting signs of hyperandrogenism and anovulation. However, there is no known cure for PCOS, and medications have only ever been used symptomatically, with a variety of adverse effects. Drugs made from natural plant products may help treat PCOS because several plant extracts have been widely recognized to lessen the symptoms of PCOS. In light of this, 72 current studies on natural products with the potential to control PCOS were examined. By controlling the PI3K/AKT signaling pathway and decreasing NF-κB and cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6), certain plant-derived chemicals might reduce inflammation. Other substances altered the HPO axis, which normalized hormones. Additionally, other plant components increased glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels to reduce radiation-induced oxidative stress. The other substances prevented autophagy by impairing beclin 1, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 - II (LC3- II). The main focus of this comprehensive review is the possibility of plant extracts as natural bio-resources of PCOS treatment by regulating inflammation, hormones, reactive oxygen species (ROS), or autophagy.