Bioactive Phytocompounds Research Articles

Phytochemical Profiling and Cytotoxic Potential of Senecio flavus n-Hexane Extract using in vitro and in silico Approaches

Background: Using natural products as potential anticancer and antimicrobial agents has gained significant attention. Methods: This study investigated the anticancer and antimicrobial properties of Senecio flavus by using MTT and well-diffusion assays, respectively. The study also examined the potential of S. flavus extracts to induce apoptosis in liver cancer cells using light and fluorescent microscopy. Gas Chromatography-Mass Spectrometry (GC-MS) was utilized to identify the phyto-compounds, which were subsequently analyzed through molecular docking using AutoDock Vina 1.1.2. Result: The difference in solvent polarity and extraction methods had a notable influence on the yield of the extracts. The saponin fraction had the highest yield (4.42%). Only the hexane extract demonstrated cytotoxic with IC50 values of 241.2 and 187.8 mg/mL for HepG2 and Huh-7 cells, respectively. Apoptotic morphological changes were observed in cells treated with the hexane extract. Additionally, apoptotic cell induction was confirmed using DAPI and AO-EB dual staining. The saponin fraction of S. flavus demonstrated antimicrobial activity, indicated by inhibition zones measuring 19 mm, 27 mm, 13 mm, 17 mm 12 mm against Acinetobacter baumannii (MDR), Acinetobacter baumannii (ATCC® BAA-747), Staphylococcus epidermidis, Staphylococcus aureus Listeria monocytogenes, respectively. GC-MS analysis identified a range of bioactive phyto-compounds within the hexane extract. The compounds (R)-3,5,8a-Trimethyl-7,8,8a,9-tetrahydronaphtho[2,3-b]furan-4(6H)-one and Tricyclo [20.8.0.0 (7,16)]triacontane, 1(22),7(16)-diepoxy- demonstrated the most favourable docking results with 4JAS and 5W1B, respectively, exhibiting a ΔG of -9.7 kcal/mol. This highlights the potential of S. flavus as a promising plant, which requires further investigation and development as a therapeutic agent.

Evaluating anti-inflammatory and anti-oxidative potentialities of the chloroform fraction of Asparagus racemosus roots against cisplatin induced acute kidney injury

Ethnopharmacological relevanceAcute kidney injury (AKI), a global public health concern that increases the risk of death, end-stage renal disease, and prolonged hospital admissions. As of this point, supportive measures like fluid resuscitation and replacement therapy for renal failure are the only treatments available for treating AKI. Asparagus racemosus (AR) also known as Shatavari, belongs to family Liliaceae and is considered exceptional in Ayurvedic medicine due to its versatility in treating and preventing a variety of illnesses. Aim of the studyThe purpose of this study is to determine the effectiveness of chloroform fraction of Asparagus racemosus (CFAR) against cisplatin (CP) induced AKI. Materials and methodsHPLC was used to analyse the presence of bioactive phytocompounds in CFAR using standard quercetin. Further LC-MS study indicated the existence of different bioacive compounds. Normal Rat Kidney (NRK-52E) cells were used to study the nephroprotective effect of CFAR. Cells were untreated, treated or cotreated with CP (20uM) and CFAR (5, 25, 50, 100, 200 and 400μg/ mL) for 24 h. After 24 h of treatment, cell viability assay and assay of apoptosis parameters were performed. The CFAR at the dose of 50mg, 100mg and 200/kg/day was administered orally for 15 days and acute kidney injury was induced in rats by intraperitoneal injection of CP (10mg/kg body weight) at the 10th day of experimentation. Biochemical studies were performed to evaluate kidney function; protein expression by western blot and mRNA expression of related gene were studied from the kidney tissues to evaluate the effects of CFAR. Histopathological analysis was done to investigate the structural abnormalities and fibrosis of renal tissues. ResultOur result reported that CFAR contain many bioactive phytomolecules having many pharmacological properties. Cell viability assay and assay of apoptosis reported that different doses of CFAR could reduced CP-induced cell death and cell apoptosis. The levels of kidney injury markers (BUN, sCr and eGFR), inflammatory markers (Interleukin-18, KIM-1, Cys-C, NF-kB and NGAL), and antioxidant markers (SOD, GSH, CAT, Nrf2 and Bcl2) and lipid peroxidation (MDA) were settled to a normal level by the oral administration of high doses (100 and 200mg/kg body weight) of CFAR after intraperitoneal injection of CP as suggested by biochemical, histopathological, protein and gene expression studies. ConclusionIn conclusion, CFAR at the high doses (100 and 200 mg/kg body weight) could able to protect the kidneys from CP induced oxidative stress and inflammation due to presence of bioactive phytomolecules that prevent the activation of oxidative stress induced signalling cascades leading to kidney damage.

Bioactive phytocompounds profiling and the evaluation of analgesic, anti-inflammatory, and antihyperglycemic potential of Argyreia capitiformis (Poir.) Ooststr.: A combined in vitro, in vivo, and computational investigations

Ethnopharmacological relevanceArgyreia capitiformis (Poir.) Ooststr. (Convolvulaceae) is traditionally used by the Chakma community in the hilly region of Bangladesh to treat minor disorders such as pain. Aim of the studyThis study intended to determine the secondary metabolites to identify bioactive compounds and evaluate antioxidant potential, in vitro anti-inflammatory and in vivo analgesic, anti-inflammatory, and antihyperglycemic activities of A. capitiformis along with in silico investigations. Materials and methodsChemical profiling was carried out using HPLC and GC-MS analysis. The analgesic effect was measured employing tail immersion and acetic acid-induced writhing methods. Following protein denaturation and formalin-induced paw edema, anti-inflammatory activity was studied. The antihyperglycemic potential was assessed using an oral glucose tolerance test (OGTT), while further mechanistic investigation was conducted using an alpha-glucosidase enzyme inhibitory assay. Simulations and molecular docking analyses were performed to ascertain the stability and binding affinities of the drug-protein complex. ResultsA. capitiformis ethanolic extract confirmed the presence of phenolics, alkaloids, flavonoids, terpenoids, tannins, gums, steroids, and reducing sugars. HPLC analysis revealed the presence of eight polyphenolic compounds, the most abundant of which was myricetin (64.10 ± 0.14 mg per 100 g dry extract). Moreover, the GC-MS analysis revealed twenty-four molecules, the most important of which was 2,4-bis (dimethylbenzyl)-6-t-butylphenol (9.19%). The concentrations of total flavonoids, total terpenoids, total phenolics, and total tannins were ascertained to be 142.48 mg QE/g, 173.1 mg UAE/g, 19.35 mg GAE/g, and 13.05 mg GAE/g, respectively. Furthermore, the plant extract had a total antioxidant capacity of 388 mg AAE/g. In the writhing assay, the plant extract suppressed writhing by 59.73% and 76.99% at the doses of 250 and 500 mg/kg, respectively, compared to the standard diclofenac Na 87.17%, and in the tail immersion assay, the plant extract displayed a maximum average reaction time of 1.94 and 2.40 s at the doses of 250 and 500 mg/kg, respectively as compared to the control tramadol 2.84 s at 60 min. In an in vitro anti-inflammatory assay, the plant extract possessed an IC50 of 95.51 μg/ml while diclofenac Na (standard drug) was found to be 69.50 μg/ml. Afterward, in vivo anti-inflammatory activity was observed in mice over a period, particularly after 3 h, the plant extract exerted maximum percent inflammation inhibitions of 36.36% and 45.45% at the doses of 250 and 500 mg/kg, respectively whereas ibuprofen the standard drug (100 mg/kg) exhibited 61.82%. The plant extract demonstrated antihyperglycemic activity, lowering blood sugar levels to 5.7 and 4.62 mM at doses of 250 and 500 mg/kg, respectively, as opposed to 8.58 mM in the control group. Meanwhile, the standard drug glibenclamide (5 mg/kg) dropped blood glucose levels to 2.38 mM in 60 min after glucose administration. Molecular docking (MD) and molecular dynamics simulation (MDS) studies support the stability of the protein complex responsible for exerting pharmacological activities. ConclusionA. capitiformis extract exhibited strong medicinal values supporting its traditional uses.

The Antitumor Potential of Sicilian Grape Pomace Extract: A Balance between ROS-Mediated Autophagy and Apoptosis.

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells' ROS rapidly increased and progressively diminished over time, in breast cancer, cells' ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.

Integrated developmental and green social work field education to control fall armyworm Infestation in maize crops in Malawi

In Malawi, fall armyworm (FAW) infestation in maize crops is a problem of public importance as it reduces maize yields and exacerbates household food insecurity. In addition to pest resistance, the use of synthetic pesticides to control FAW negatively affects the health of farmers and the environment. Biochemical pesticides from plants contain naturally non-toxic chemotypes and are effective in controlling pests. Tephrosia vogelii plants contain these bioactive phytocompounds that have pesticidal properties. Geographical location and plant species influence the occurrence of phytocompounds in Tephrosia vogelii. Farmers in Sub Sahara-Africa are using Tephrosia vogelii as a pesticide but there are mixed research findings regarding its effectiveness in controlling FAW pests. This study was informed by developmental and Green Social Work frameworks to compare the effectiveness of Tephrosia vogelii leaves extracts, Belt 480 SC, and soap solution in controlling FAW in maize gardens. The study employed a randomized complete block design with four replication gardens and was conducted from November 2022 to March 2023. A social work field education student was assigned to coordinate the project. The study affirmed that the sampled Tephrosia vogelii leaf extracts contained pesticidal chemotypes. The results of field gardens suggest that Tephrosia vogelii leaf extracts have similar potency to Belt SC 480 chemical pesticide. It has been identified that Boom detergent soap is not as effective as Tephrosia vogelii leaf extracts. The study has social work field education implications for empowering practicum students to gain community mobilization skillsets, to participate in environmental justice advocacy, and to uphold social work values.

Natural fermentation of fresh Jasmine flowers inspired the development of a biotechnological ingredient with global anti-ageing properties.

This study focused on the development of a new-to-world ingredient harnessing the natural potential of fresh Jasminum grandiflorum flowers to self-ferment by its phytobiome revealing flower content. Analytical investigations were conducted to highlight specific phytocompounds generated during the natural fermentation of flowers in comparison to a conventional extraction. The synergy with another extraction technology maximized the generation of biocompounds for an interesting efficacy. Jasmine extract was elaborated by combining two patented technologies: the phytofermentology™, inspired by plant-microorganisms interaction and designed to develop ingredients obtained by natural fermentation of the vegetal using its own phytobiota; and the PSR™ technology allowing the extraction of bioactive phytocompounds such as small RNAs from plants. Analytical investigations of Jasmine extract highlighted uniqueness and richness of the phytocompound profiles, such as organics acids and phenolic compounds, markers of fermentation only obtained after phytofermentology in comparison to conventional extraction. Jasmine extract has the particularity to contain jasmintides, flower small peptides belonging to the family of cysteine-rich peptides (CRPs). Antioxidant and global anti-ageing properties were investigated in cell-free assays demonstrating interesting results: about 20% scavenging of free radicals from 0.5% of Jasmine extract and protection from DNA damage of 26% in comparison to a stressed control. Phytofermentology™ technology combined with PSR™ technology, meant to be respectful of the environment, allowed to development of biofunctionals very close to nature with a unique analytical signature as Jasmine extract, using the potential of fresh flowers phytobiota to self-ferment. The efficacy of the ingredient on global antioxidation and anti-ageing via hyaluronidase/tyrosinase inhibitions was highlighted by cell-free evaluation assays. Further and complementary studies should be conducted to confirm the bioefficacy of this ingredient with invitro / exvivo assays.

Comparative analysis of phytochemical properties of extracts obtained from flowers and leaves of Astragalus angustifolius collected from different locations

Plants containing phenolic secondary metabolites such as tannins and flavonoids are of great interest due to their antioxidant and antimicrobial effects on health. Many species belonging to the Astragalus genus possess promising bioactive phyto-compounds and are used in folk medicine worldwide. In this study, extracts were obtained using two different solvents (ethanol and methanol) from the flowers and leaves of Astragalus angustifolius collected from two different locations in Kahramanmaraş. The antioxidant and antimicrobial activities of these extracts were compared, along with their total phenolic and flavonoid contents. Additionally, the fixed oil content of the extracts was examined using GC-MS analysis, revealing 8 different fatty acid components. The main fatty acid components of the plant extracts were found to be linoleic, oleic, and gamma-linolenic acids in high abundance at both locations. In the methanol extracts of A. angustifolius, total phenolic content ranged from 14.82 to 15.47 mg GAE/g dw in leaves and from 4.38 to 5.30 mg GAE/g dw in flowers. Similarly, flavonoid content ranged from 8.14 to 9.26 mg QE/g dw in leaves and from 5.08 to 5.20 mg QE/g dw in flowers. Leaves exhibited higher phenol and flavonoid content and antioxidant activity compared to flowers. Moreover, methanol was observed to be more successful than ethanol in retrieving the bioactive content of the plant material. This conclusion was confirmed by both antioxidant capacity tests such as FRAP and IC50 values, and the difference in phenol and flavonoid levels between leaves and flowers. Antimicrobial activity determination using the well-diffusion method showed that A. angustifolius leaf extracts had a broad spectrum of effects on test microorganisms.

Screening of Phosphoinositide-3 Kinase Inhibitors from Argemone mexicana Leaves

Background: Phosphoinositide 3 kinase belongs to the enzyme family which is responsible for the development of cellular trafficking and uncontrolled cellular division which in turn to cancer metastasis. Activation of the PI3k-Akt-mTOR pathway tends to promote oncogenesis in Lung Cancer and its mutation leads to resistance in EGFR tyrosine kinase inhibitors. Objective: Inhibition of the initial PI3k receptor through natural bioactive phytocompounds from Argemone mexicana that may prevent the side effects caused by the synthetic medication and improve the patient's life quality as natural medicine. Method: According to the previous research we did the Bioactive phytochemical screening from the methanol extract (AME) and powder (AMP) of A. mexicana leaf by analysing the GC-MS (Agilent), UPLC-QTOF-ESI-MS (Waters India Pvt Limited). Analyzed phytochemicals from the studies were subjected to molecular docking analysis using SeeSAR 9.2 software against PI3K (PDP ID: 4FA6) receptor. Result: GC-MS revealed 40 compounds including Cryptopine (17.5), beta-sitosterol (9.57), and Protopine (8.6) were found as major compounds. LC-MS analysis showed the presence of major compounds with 13 elements compared to the literature survey in both positive and negative ESI ranges. 29 compounds from the GC-MS and LC-MS were selected for analyzing the interaction between the cancer receptor-ligand complex according to the binding strategy. Conclusion: Phytoconstituents such as Galactitol, Succinic acid and N-feruloyltryamine from A. mexicana showed good binding affinity range and maximised hydrogen bonding that may assure possessing anticancer effect by controlling the PI3K pathway. This study would lead a major role in the preliminary screening of Drug Targets against the PI3K receptor.

Bioactive Phyto-Compounds with Antimicrobial Effects and AI: Results of a Desk Research Study.

Resistance of microorganisms to antibiotics represents a formidable global challenge, manifesting in intricate public health ramifications including escalated mortality rates and augmented healthcare costs. The current efforts to manage antimicrobial resistance (AMR) are limited mainly to the standard therapeutic approaches. The aim of this study is to present and analyze the role of artificial intelligence (AI) in the search for new phyto-compounds and novel interactions with antimicrobial effects. The ambition of the current research study is to support researchers by providing summarized information and ideas for future research in the battle with AMR. Inevitably, the AI role in healthcare is growing exponentially. The reviewed AI models reveal new data on essential oils (EOs) as potential therapeutic agents. In terms of antibacterial activity, EOs show activity against MDR bacteria, reduce resistance by sensitizing bacteria to the action of antibiotics, and improve therapeutic efficiency when combined with antibiotics. AI models can also serve for the detailed study of other therapeutic applications of EOs such as respiratory diseases, immune diseases, neurodegenerative diseases, and oncological diseases. The last 5 years have seen an increasing application of AI in the search for potential plant sources to control AMR. For the time being, the application of machine-learning (ML) models is greater in the studies of EOs. Future attention of research teams may also be directed toward a more efficient search for plant antimicrobial peptides (PAMPs). Of course, investments in this direction are a necessary preface, but the excitement of new possibilities should not override the role of human intelligence in directing research processes. In this report, tradition meets innovation to address the "silent pandemic" of AMR.

In Silico, In Vitro and Ex Vivo Evaluation of the Antihyperglycaemic, Antioxidant and Cytotoxic Properties of Coccinia grandis L. Leaf Extract.

Coccinia grandis L. is traditionally used for the treatment of diabetes mellitus. Since the scientific evidence and mechanism of action have not yet been extensively investigated, this study aims to evaluate the antidiabetic and cytotoxic effects together with the optimisation and development of a scale-up process design for higher yields of bioactive phytocompounds from C. grandis. The in silico study was conducted to predict the binding affinity of phytocompounds of C. grandis for α-amylase and α-glucosidase enzymes involved in the pathophysiology of diabetes with pharmacokinetic assessment. Response surface methodology was used to determine the optimum total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC) and antioxidant activities (DPPH and FRAP) in 17 different experimental runs in which the parameters of microwave-assisted extraction such as temperature (50-70 °C), power (400-1000 W) and time (15-45 min) were varied. The phytocompounds were purified and identified using column chromatography, thin-layer chromatography (TLC), UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and liquid chromatography-mass spectrometry (LC-MS). The in vitro antidiabetic activity was determined by α-amylase and α-glucosidase enzymatic inhibitory assays, while cytotoxic investigations were done by measuring haemolytic activity, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and chorioallantoic membrane (CAM) assays. The reported major bioactive compounds have shown an excellent binding affinity for α-amylase and α-glucosidase enzymes in the range of -14.28 to -36.12 kJ/mol with good pharmacokinetic properties and toxicities ranging from low to medium. The bioactive constituents such as total phenols, total flavonoids, total tannins and antioxidant activities such as DPPH and FRAP were found to be high and dependent on the optimised microwave-assisted extraction parameters such as temperature, time and power: 55 °C, 45 min and 763 W, respectively. Sixteen compounds were identified by FTIR and LC-MS spectra in the plant sample after preliminary identification, purification and TLC. The percentage of enzyme inhibition depended on the concentration of the extract (7.8-125.0 µg/mL) and was higher than that of acarbose. The haemolytic activity was in accordance with ISO standards and low toxicity was observed in the MTT and CAM assays in the range of 7.8-125.0 µg/mL, suggesting its potential use as an antidiabetic drug and for functional food development. The results of the study open up new opportunities for researchers, scientists and entrepreneurs in the food and pharmaceutical sectors to develop antidiabetic foods and medicines that help diabetics to better control their condition and maintain overall health.

Blueberry extract and its bioactive compounds mitigate oxidative stress and suppress human lung cancer cell (A549) growth by modulating the expression of p53/EGFR/STAT3/IL6-mediated signaling molecules.

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of -9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of -8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre-dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications.

In-vitro antioxidant and anti-inflammatory potential along with p.o. pharmacokinetic profile of key bioactive phytocompounds of Snow Mountain Garlic: a comparative analysis vis-à-vis normal garlic.

Snow mountain garlic (SMG) is a trans-Himalayan medicinal plant used in the traditional medicine system for several ailments, including inflammatory arthritis. Research studies are insufficient to validate its folk medicinal applications. In the present study, the comparative abundance of its key bioactive phytocompounds, viz., S-allyl-L-cysteine (SAC), alliin, and S-methyl-L-cysteine (SMC) against normal garlic were assessed using the LC-MS/MS-MRM method. In addition, the study also explored the antioxidant and anti-inflammatory potency of crude extract of SMG and purified signature phytocompounds (i.e., SMC, SAC, and alliin) in comparison with normal garlic and dexamethasone in LPS-stimulated RAW264.7 macrophage cells. The LC-MS/MS-MRM study revealed significant differences among SMG and normal garlic, viz., alliin 22.8-fold higher in SMG, and SMC could be detected only in SMG. In the bioassays, SMG extract and purified signature phytocompounds significantly downregulated oxidative damage in activated macrophages, boosting endogenous antioxidants' activity. SMG extract-treated macrophages significantly suppressed NF-κB expression and related inflammatory indicators such as cytokines, COX-2, iNOS, and NO. Notably, the observed anti-inflammatory and antioxidant bioactivities of SMG extract were comparable to signature phytocompounds and dexamethasone. In addition, SAC being uniformly found in SMG and normal garlic, its comparative pharmacokinetics was studied to validate the pharmacodynamic superiority of SMG over normal garlic. Significantly higher plasma concentrations (Cmax), half-life (t1/2), and area under curve (AUC) of SAC following SMG extract administration than normal garlic validated the proposed hypothesis. Thus, the abundance of bioactive phytocompounds and their better pharmacokinetics in SMG extract might be underlying its medicinal merits over normal garlic.

Targeting Peroxisome Proliferator-Activated Receptor-β/δ, Reactive Oxygen Species and Redox Signaling with Phytocompounds for Cancer Therapy.

Significance: Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. Recent Advances: Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression. Critical Issues: Modulation of PPAR-β/δ activity has been suggested as a potential therapeutic strategy for cancer management. This review focuses on the ability of bioactive phytocompounds to impact reactive oxygen species (ROS) and redox signaling by targeting PPAR-β/δ for cancer therapy. The rise of ROS in cancer cells may play an important part in the initiation and progression of cancer. However, excessive levels of ROS stress can also be toxic to the cells and cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS insults induced by exogenous agents, such as phytocompounds and therapeutic agents. Therefore, redox modulation is a way to selectively kill cancer cells without causing significant toxicity to normal cells. However, use of antioxidants together with cancer drugs may risk the effect of treatment as both act through opposite mechanisms. Future Directions: It is advisable to employ more thorough and detailed methodologies to undertake mechanistic explorations of numerous phytocompounds. Moreover, conducting additional clinical studies is recommended to establish optimal dosages, efficacy, and the impact of different phytochemicals on PPAR-β/δ.

Exploring the therapeutic mechanism of potential phytocompounds from Kalanchoe pinnata in the treatment of diabetes mellitus by integrating network pharmacology, molecular docking and simulation approach

Since ancient times, bioactive phytocompounds from different parts of medicinal plants have been used to heal various disease ailments and they are now regarded as a valuable source of disease prevention globally.Kalanchoe pinnatais a member of the Crassulaceae family; it has a long history of usage in traditional ayurvedic treatment. Analysis of bioactive compounds for their potential anti-type-2 diabetes mellitus (T2DM) mechanism along within-vitroandin-silicoapproaches was studied in the present research. The alpha-amylase and alpha-glucosidase inhibitory activity of methanolic extract of Kalanchoe pinnata (α-amylase: IC50 29.50 ± 0.04 μg/ml; α-glucosidase IC50 32.04 ± 0.35 μg/ml) exhibit a high degree of similarity to the standard drug acarbose (IC50 35.82 ± 0.14 μg/ml). Different biological databases were used to list phytocompounds from the plant, and ADME analysis using swissADME was carried out to screen compounds that obeyed the Lipinski rule of 5 and were employed further. STRING and KEGG pathway analysis was performed for gene enrichment analysis followed by network pharmacology to identify key target proteins involved in DM. AMY2A, NOX4, RPS6KA3, ADRA2A, CHRM5, and IL2 were identified as core targets for luteolin, kaempferol, alpha amyrin, stigmasterol compounds by modulating neuroactive ligand interaction, P13-AKT, MAPK, and PPAR signaling pathways. Molecular docking was performed to study the binding affinity among bioactive compounds ofK. pinnataagainst aldose reductase, alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase IV. Alpha-amylase-friedelin [FRI] and alpha-amylase-acarbose [STD] complexes were subjected to molecular simulation for a 200 ns duration that depicted the stability of the compounds and proteins. In the current study, employing dual approach in-silico and in-vitroenzyme assays has yielded a comprehensive and strong understanding of its potential therapeutic properties, making a significant step towards the development of novel anti-diabetic treatment.

A Comprehensive Review on the Traditional Uses, Phytochemical Compositions and Pharmacological Properties of an Ethnomedicinal Herb, Paederia foetida

Background:: Paederia foetida L. (Family – Rubiaceae) is a common herb found available in the temperate and tropical Asia. The ethnomedicinal applications of this plant are widely elaborated In Chinese Traditional Medicine, Ayurveda, and other ancient scriptures throughout the world. Different ethnic groups use this plant in the treatment of alimentary and digestive disorders, bone related diseases like rheumatoid arthritis, bone fractures as well as in the ailments of diabetes, coughs, asthma, itches, wounds, body ache, toothache, cancer etc. Objectives:: This comprehensive review aims to provide an insightful understanding of traditional uses, chemical composition, and pharmacological properties of P. foetida (from 1976 up to 2023), which may provide a foundation for further study and for the proper utilization of P. foetida resources. Methods:: Literature survey was conducted using known databases and the relevant keywords. Results:: P. foetida has been widely used in Chinese traditional medicine (CTM) for the treatment of dyspepsia, jaundice, pains, diarrhea and others. Several ethnic groups throughout the world used this plant to cure common health complaints namely, abdominal pain, gastritis, dysentery, diarrhoea, constipation, joint pain, etc. A total of 24 bioactive phytocompounds, such as asperuloside, paederosidic acid, sitosterols, stigmasterol, campesterol, ellagic acid, iridoids, ursolic acid, epifriedelinol, and others are reported to possess antiulcer, antidiarrheal, antihyperglycemic, antioxidant, antitussive, anthelmintic, and hepatoprotective activities. Conclusion:: The present review not only summarizes the alternative approaches using this herb by ethnic people for treating various disorders, but also focuses on the latest scientific investigations to elucidate different bioactivities of this plant, thereby facilitating the understanding of its correlation with contemporary pharmacology. However, till date, very few studies elucidated the biological properties of these phytochemicals that were isolated exclusively from this particular plant. Moreover, the correlation between phytocompounds from P. foetida and its pharmacological activities aiming towards clinical drug development is still lacking. Finally, further research should be oriented towards determining the optimal dosage and toxicological limits, and thereby providing guidance for clinical applications.

Immunomodulatory Phytocompounds from Withania somnifera (L.) Dunal (Ashwagandha) Against COVID-19

Withania somnifera is a famous medicinal plant. It is popularly known as Aswagandha. This plant has been in use in Ayurveda and Unani medicine for ages. The medicinal plant has immense medicinal properties. The plant is rich in potent medicinal phytocompounds. These phytocompounds are known to have potent antioxidant, antiviral, antibacterial and immunomodulatory efficacies. Our immune system is the key player in n fighting back any kind of pathogeni attack on us. Withania somnifera extract and certain isolated phytocompounds from the plant are known to boost our immune system. Studies show that the mechanisms of immunomodulatory actions of the bioactive phytocompounds from Withania somnifera are by affecting the various cellular signaling pathways. These primarily involve the signaling pathways associated with the receptors present on the vital immune cells like the dendritic cells, T-cells and B-cells. Thus, some of the compounds of Withania suppress or activate certain components of the innate and adaptive immune system. Unlike synthetic adjuvants, the natural plant derived phytocompounds and their derivatives, as those from the Withania sp. are free from such risk factors. A strong immune system is the best possession to fight back invasions by microbes like bacteria and viruses like the SARS-CoV-2. Detailed and compact knowledge of the compounds from Withania sp. and their mechanism of modulating and impacting our immune system may make the ways for development of new supportive therapies against almost all different types of diseases including COVID 19.

GC–MS analysis, molecular docking, and pharmacokinetic studies of Multidentia crassa extracts’ compounds for analgesic and anti-inflammatory activities in dentistry

Plant extracts have been useful for oral health or dentistry. However, only a few evidence-based justifications exist. This study evaluated Multidentia crassa (Hiern) Bridson & Verdc, one of the oral health-used plants in Malawi. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FT-IR) identified the extracts’ compounds. The pharmacokinetics of the identified compounds were studied using pkCSM and SwissADME, and molecular docking studies were used to identify potential drug candidates for oral health by predicting the binding affinity of the compounds to cyclooxygenases, interleukin-1 beta receptors, odontoblast cold sensor proteins, and purinergic receptor P2X3. FT-IR analysis showed characteristic peaks of phenols, carboxylic acids, alkenes, alkyl halides, amines, esters, ethers, aromatics, and lipids. GC–MS results showed the presence of 58 bioactive phytocompounds, some of which have various pharmacological activities relevant to oral health. Molecular docking further validated stigmastan-3,5-diene’s potency for analgesic and anti-inflammatory purposes. Based on a literature review, this is the first report on the bioactive compounds of M. crassa extracts showing analgesic and anti-inflammatory effects. This study's results can lead to new herbal and conventional medicines. Therefore, we recommend in vivo and in vitro studies to elucidate the pharmacological effects of the plant extracts.

Exosomal microRNA profiling revealed enhanced autophagy suppression and anti-tumor effects of a combination of compound Phyllanthus urinaria and lenvatinib in hepatocellular carcinoma.

Compound Phyllanthus urinaria (CP), a traditional Chinese herbal remedy, possesses strong anti-cancer effects and is extensively employed in the clinical management of hepatocellular carcinoma (HCC). While lenvatinib and other oral tyrosine kinase inhibitors have been authorized as initial treatments for advanced unresectable HCC, the survival of patients is ultimately restricted due to the gradual development of drug resistance. Fortunately, the co-administration of CP and lenvatinib holds promise for anti-cancer applications. Our objective was to understand the molecular-level mechanisms of bioactive phytocompounds in CP, in order to explore the anti-HCC effects of combining CP and lenvatinib treatment and reveal the underlying mechanisms. Furthermore, we discovered new miRNAs associated with autophagy that are common to both HepG2-derived exosomes and HepG2 cells. These miRNAs play a role in the advancement of HCC and were identified through the utilization of CP and lenvatinib. To assess the anti-HCC effects of CP in combination with lenvatinib, both an in vitro CCK-8 assay and an in vivo xenograft model assay were performed. TEM, NTA, and nano-flow cytometry were employed for the identification of isolated exosomes. To ascertain the miRNA expression patterns in HepG2 cells and HepG2-derived exosomes, miRNA-sequencing analysis was conducted. Further investigation involved the use of real-time PCR, examination of the fusion protein GFP-mRFP-LC3, TEM analysis, and western blotting. In vitro and in vivo, the combination of CP and lenvatinib showed a stronger and more powerful impact on HCC compared to either CP or lenvatinib alone. The combination of CP and lenvatinib had a significant impact on autophagy-related miRNAs in HepG2-derived exosomes and HepG2 cells, as demonstrated by cellular and exosomal miRNA sequencing. Additional tests indicated that the increased inhibition of autophagy in HepG2 cells subjected to CP treatment, as well as the combination of CP and lenvatinib, was accomplished through the regulation of Beclin-1, LC3-II, and P62 expression. In conclusion, our results indicate that the combination of CP and lenvatinib can effectively inhibit HCC by promoting the exosome-mediated suppression of autophagy. This novel therapeutic option is highly efficient and durable, making it a promising treatment for HCC. Moreover, the miRNAs that are differentially expressed and associated with exosome-mediated autophagy, which have been discovered in this study, could potentially be targeted for clinical treatment of HCC.

Phytochemically analysed extract of Ageratina adenophora (Sprengel) R.M.King & H. Rob. initiates caspase 3-dependant apoptosis in colorectal cancer cell: A synergistic approach with chemotherapeutic drugs

Ethnopharmacological relevanceAgeratina adenophora (Sprengel) R.M.King & H.Rob. has been used as traditional indigenous medicine all across the globe for its diverse therapeutic applications such as anticancer, analgesic, antipyretic, thermogenic, antiseptic, antimicrobial as well as astringent. The various ethnic groups of India use plant parts to treat cuts and wounds, venomous insect bites, skin lesions, blisters, scabies and other skin irritations, gastritis and indigestion problems, cough, stomach ache and dysentery. The Portuguese traditionally extract the juice from the plant and use it for cancer, diabetes, liver disorder, gallbladder and stomach ailments. Nigerian healers use different parts of the plant to treat diabetes, fever and inflammation. Aim of the studyThe aim of this study is to investigate the cytotoxic potential of A. adenophora hydroalcoholic leaves extract (AHL) on Colorectal cancer (CRC) cell lines (HCT-116, HCT-15 and HT-29), synergistic potential with chemotherapeutic drugs 5FU and Cisplatin as well as reactive oxygen species (ROS) generation, based on the sample collected from Mao district of Manipur, India. Identification of bioactive phytocompounds in AHL was also performed by HRLCMS. MethodsThe AHL was evaluated for its cytotoxic as well as antiproliferative activities by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay, clonogenic and cell migration assays. The total phenolic content (TPC) and total flavonoid content (TFC) were quantified by Folin-ciocalteu and Aluminium chloride assays respectively. Caspase 3 activation was evaluated using Caspase-3 Assay Kit. Apoptosis detection by flow cytometry was carried out using annexin V-FITC/PI apoptosis detection kit. The apoptotic cells were also visualized by Giemsa and 4′,6-Diamidino-2-phenylindole (DAPI) staining. The intracellular Reactive oxygen species (ROS) generation was also evaluated using fluorescent probe 2′,7′-dichlorodihydrofluorescein di-acetate (H2DCFDA) in flow cytometry. The combination effects of AHL with chemotherapeutic drugs 5FU and Cisplatin were also evaluated. The identification of phytochemical constituents of AHL were analysed by HR-LCMS. ResultsThe AHL induced cytotoxic activity significantly in HCT-116 with IC50 of 65.65 ± 2.10 μg/mL, but non-cancerous cell HeK-293 was least cytotoxic. Colony formation and cell migration were inhibited in a dose and time dependent manner. The cell morphology upon AHL treatment was significantly altered with apoptotic features. The extract was rich in total phenolic (82.09 ± 0.35mgGAE/g) and total flavonoid (58.31 ± 0.55 mgQAE/g) contents. AHL induced apoptosis as detected by AnnexinV/PI, via activation of caspase 3 and elevated production of Reactive oxygen species (ROS). AHL in combination with 5FU and Cisplatin acts synergistically and potentiates the therapeutic properties of the extract. Sesquiterpenes, phenolic as well as flavonoid derivatives with anticancer properties were detected in AHL by HRLCMS, and these phytoconstituents may be attributed for anticancer property of AHL. ConclusionThe present study evaluates the effectiveness of AHL against Colorectal cancer cell lines. AHL is cytotoxic and induces apoptosis in HCT-116 cells by caspase 3 activation and increased ROS production that can be attributed to sesquiterpenoids. Thus, the plant A. adenophora has therapeutic potential for Colorectal cancer and can be further exploited for developing anticancer drug.

Cytotoxicity and gene expression studies in understanding the mechanism on antimycobacterial properties of methanolic leaf extract of Acalypha indica Linn.

Despite the availability of effective antituberculosis medication, tuberculosis (TB) remains a serious global health concern, raising the demand for low-after effect drug alternative. This study aims to explore the anti-mycobacterial potency of Acalypha indica Linn. on Mycobacterium tuberculosis using Mycobacterium smegmatis as a model and thereby uncover its mechanism. Characterization of bioactive phytocompounds and their cumulative effects were studied through both biochemical and molecular approaches. The antimycobacterial efficacy was screened by cell viability assay and IC50. FE-SEM and qRT-PCR were used to study the effect of A. indica leaf methanolic extract (AILME) on cell integrity and mycolic acid synthesis pathway. This study reports AILME to be the most effective solvent-extract combination which showed >40 % cell inhibition from 25 µg mL−1 onwards at 24 hr. AILME showed >80 % antioxidant potential, lowest IC50 of 48.24 µg mL−1 and a MIC value of 200 µg mL−1 at 24 hr. The FE-SEM analysis of the AILME treated bacterial cells showed significant morphological damage which supports the results of antimycobacterial activity. The gene expression study revealed that AILME inhibited the expression of inhA and mtrA genes involved in mycolic acid biosynthesis pathway and cell wall integrity, respectively. The bioactive phytocompounds characterised through GCMS and HR-LCMS revealed about nineteen potent anti-TB compounds like malic acid, catechin, pyrrolidine, hexadecanoic acid, quercetin etc. that might supervise the role behind the antimycobacterial effect of the herb. This study reveals that AILME possesses strong antimycobacterial action by impeding the formation of mycolic acid biosynthesis pathway and disorganization of cell wall. Presence of anti-TB phytocompounds in abundance suggest its potential chemotherapeutic nature against M. tuberculosis.