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 pinnata is 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 with in-vitro and in-silico approaches 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 of K. pinnata against 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-vitro enzyme 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.

Exploring the Potential of Phytocompounds for Targeting Epigenetic Mechanisms in Rheumatoid Arthritis: An In Silico Study Using Similarity Indexing.

Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

In Vitro Antibacterial Activity of Green Synthesized Silver Nanoparticles Using Azadirachta indica Aqueous Leaf Extract against MDR Pathogens.

Rice is the most important staple food crop feeding more than 50% of the world's population. Rice blast is the most devastating fungal disease, caused by Magnaporthe oryzae (M. oryzae) which is widespread in rice growing fields causing a significant reduction in the yield. The present study was initiated to evaluate the effect of green synthesized silver nanoparticles (AgNPs) on the biochemical constituents of rice plants infected with blast. AgNPs were synthesized by using Azadirachta indica leaf extract and their characterization was performed using UV-visible spectroscopy, particle size analyser (PSA), scanning electron microscope (SEM), and X-ray diffraction (XRD) which confirmed the presence of crystalline, spherical shaped silver nanoparticles with an average size of 58.9 nm. After 45 days of sowing, artificial inoculation of rice blast disease was performed. After the onset of disease symptoms, the plants were treated with AgNPs with different concentrations. Application of nanoparticles elevated the activity of antioxidative enzymes such as superoxide dismutase, catalase, peroxidase, glutathione reductase, and phenylalanine ammonia-lyase compared to control plants, and total phenol and reducing sugars were also elevated. The outcome of this study showed that an increase in all biochemical constituents was recorded for A. indica silver nanoparticles-treated plants. The highest values were recorded in 30 ppm and 50 ppm AgNPs-treated plants, which showed the highest resistance towards the pathogen. Green synthesized AgNPs can be used in future for disease control in susceptible varieties of rice. The synthesized AgNPs using A. indica leaf extract have shown promising antibacterial activity when tested against 14 multidrug-resistant (MDR) bacteria comprising Gram-negative bacteria Escherichia coli (n = 6) and Klebsiella pneumoniae (n = 7) with a good zone of inhibition diameter, tested with the disc diffusion method. Based on these findings, it appears that A. indica AgNPs have promise as an antibacterial agent effective against MDR pathogens.

Synthesis and Characterization of Silver Nanoparticles from Rhizophora apiculata and Studies on Their Wound Healing, Antioxidant, Anti-Inflammatory, and Cytotoxic Activity.

Silver nanoparticles (AgNPs) have recently gained interest in the medical field because of their biological features. The present study aimed at screening Rhizophora apiculata secondary metabolites, quantifying their flavonoids and total phenolics content, green synthesis and characterization of R. apiculata silver nanoparticles. In addition, an assessment of in vitro cytotoxic, antioxidant, anti-inflammatory and wound healing activity of R. apiculata and its synthesized AgNPs was carried out. The powdered plant material (leaves) was subjected to Soxhlet extraction to obtain R. apiculata aqueous extract. The R. apiculata extract was used as a reducing agent in synthesizing AgNPs from silver nitrate. The synthesized AgNPs were characterized by UV-Vis, SEM-EDX, XRD, FTIR, particle size analyzer and zeta potential. Further aqueous leaf extract of R. apiculata and AgNPs was subjected for in vitro antioxidant, anti-inflammatory, wound healing and cytotoxic activity against A375 (Skin cancer), A549 (Lung cancer), and KB-3-1 (Oral cancer) cell lines. All experiments were repeated three times (n = 3), and the results were given as the mean ± SEM. The flavonoids and total phenolics content in R. apiculata extract were 44.18 ± 0.086 mg/g of quercetin and 53.24 ± 0.028 mg/g of gallic acid, respectively. SEM analysis revealed R. apiculata AgNPs with diameters ranging from 35 to 100 nm. XRD confirmed that the synthesized silver nanoparticles were crystalline in nature. The cytotoxicity cell viability assay revealed that the AgNPs were less toxic (IC50 105.5 µg/mL) compared to the R. apiculata extract (IC50 47.47 µg/mL) against the non-cancerous fibroblast L929 cell line. Antioxidant, anti-inflammatory, and cytotoxicity tests revealed that AgNPs had significantly more activity than the plant extract. The AgNPs inhibited protein denaturation by a mean percentage of 71.65%, which was equivalent to the standard anti-inflammatory medication diclofenac (94.24%). The AgNPs showed considerable cytotoxic effect, and the percentage of cell viability against skin cancer, lung cancer, and oral cancer cell lines was 31.84%, 56.09% and 22.59%, respectively. R. apiculata AgNPs demonstrated stronger cell migration and percentage of wound closure (82.79%) compared to the plant extract (75.23%). The overall results revealed that R. apiculata AgNPs exhibited potential antioxidant, anti-inflammatory, wound healing, and cytotoxic properties. In future, R. apiculata should be further explored to unmask its therapeutic potential and the mechanistic pathways of AgNPs should be studied in detail in in vivo animal models.

The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms.

Background: Epilepsy is a neurodegenerative condition characterized by uncontrollable convulsions caused by a misalignment of the central nervous system's inhibitory and excitatory branches. Vateria indica is a medicinal herb with anti-inflammatory, anthelmintic, antiulcer, antitumor, and anticancer properties. Objectives: To investigate the antiepileptic activity of Vateria indica using maximal electrical shock (MES), pentylenetetrazole (PTZ), and isoniazid (INH) induced experimental animal models. Methodology: Vateria indica bark was subjected to Soxhlet extraction using ethanol and quantitative and qualitative analysis was performed. The antiepileptic activity of Vateria indica bark extract (VIE) was investigated using different animal models in mice. GABA levels in the brain and antioxidant capacity in vitro were estimated. Results: Treatment of mice with VIE significantly reversed the MES-induced convulsions, which was reflected by the decrease in the duration (sec) of all the phases of MES-induced convulsions, with an increment in the GABA levels. In the PTZ and INH models, pretreatment with VIE delayed the latency to clonic convulsions (p 0.001), reduced the intensity and duration of clonic convulsions, and reduced the mortality rate in the treatment groups in a dose-dependent manner. VIE intervention dose-dependently restored brain GABA levels. VIE also exhibited significant in-vitro antioxidant activity. Conclusion: Overall, the findings imply that Vateria indica has substantial antiepileptic activities, mediated by positive GABAergic neurotransmission and antioxidant capabilities. To summarize, Vateria indica may provide adequate protection against epileptic seizures, suggesting that it could be used to treat petitmal and grandmal epilepsy. We plan to provide pure lead compounds derived from Vateria indica in the future in order to better understand the role it could play in the development of natural anticonvulsant drugs.

Characterization of Bioactive Compounds from Acacia concinna and Citrus limon, Silver Nanoparticles' Production by A. concinna Extract, and Their Biological Properties.

The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.

Topical Application of Premna integrifolia Linn on Skin Wound Injury in Rats Accelerates the Wound Healing Process: Evidence from In Vitro and In Vivo Experimental Models.

Background: When the skin and tissues within the body are injured, the healing process begins. Medicinal herbs have been used to cure wounds since time immemorial. The antimicrobial and antioxidant activity possessed by P. integrifolia may accelerate wound healing. Objectives: To assess the wound healing activity of Premna integrifolia extract (PIE) by employing in-vivo experimental animal models and an in-vitro migration scratch assay. Furthermore, to assess its cytotoxicity using the MTT assay. Methods: Wistar albino rats were used for the in vivo wound healing models. The animals were divided into four groups at random: Group I was untreated. Group II was vehicle control (ointment base). Group III was PIE ointment (5% W/W). Group IV was standard (povidone-iodine ointment) (5% W/W). The ointments were applied directly to the wounds as described above until they healed completely. The wound contraction percentage and tensile strength were calculated. The MTT test was used to determine the viability of the test extract against the fibroblast cells. The scratch assay was used in vitro to determine the wound healing potential of the test drug. P ≤ 0.05 values were considered statistically significant. Results: Premna integrifolia extract did not possess any noticeable cytotoxicity to the cell line and showed an IC50 of 185.98 µg/ml. The wound contraction potential of PIE ointment-treated animals was considerably greater (P ≤ 0.001) on days 4, 8, 12, 16, and 20 when compared to the control group. The percentage of wound contraction on day 20 was 99.92% in PIE-treated animals compared to 83.23% in untreated animals. Compared to the untreated group, the duration of full epithelization was significantly (P ≤ 0.01) shorter in the test group. When compared to the incision control group, the animals treated with PIE ointment had significantly higher (P ≤ 0.001) tensile strength. In addition, animals given the test drug had a significant (P ≤ 0.001) increase in total protein and hydroxyproline. In the in vitro scratch assay, test drug-treated cells demonstrated greater cell migration. Histology images confirmed that the test drug-treated group had epithelial tissue proliferation and keratinization. Conclusion: The current study found that Premna integrifolia improved wound healing activity both in vitro and in vivo. These findings indicate that Premna integrifolia extract has wound-healing potential and could be a viable source of nutraceuticals with wound-healing properties.

Enhanced antinociceptive activity of Nigella sativa oil after its combined treatment with honey in rats.

Antinociceptive activity of honey and Nigella sativa (N. sativa) oil are well known. Therefore, aim of this study was to investigate the antinociceptive effect of N. sativa oil and its concurrent administration with honey in rats. The tested animals were randomized into 5 groups: Group (1) Normal saline (0.2ml, p.o.); Group (2) N. sativa oil (1gm/kg, p.o.); Group (3) honey (1gm/kg, p.o.); Group (4) N. sativa oil (1gm/kg, p.o.) + honey (1gm/kg, p.o.): Group (5) pethidine (20mg/kg, S.C.) as positive standard. The antinociceptive activity was tested using radiant heat and tail immersion tests. Antioxidant potential was determined by using in-vitro antioxidant assays. Our findings showed that N. sativa oil and honey have antinociceptive effect, the antinociceptive effect appeared after 30 and 60min of administration and declined after 120 and 180 min. Combined administration of N. sativa oil with Honey increased the antinociceptive effect by 20 to 30% in all models. In addition, the antinociceptive effect of the combination reduced the time for onset of action as well as prolonged its duration of action. In conclusion, combined treatment of N. sativa oil with honey increased its antinociceptive activity, showed faster onset of action and prolonged its duration, the fact that can be utilized in the management of painful conditions in humans.

Plant-Based Synthesis of Gold Nanoparticles and Theranostic Applications: A Review.

Bionanotechnology is a branch of science that has revolutionized modern science and technology. Nanomaterials, especially noble metals, have attracted researchers due to their size and application in different branches of sciences that benefit humanity. Metal nanoparticles can be synthesized using green methods, which are good for the environment, economically viable, and facilitate synthesis. Due to their size and form, gold nanoparticles have become significant. Plant materials are of particular interest in the synthesis and manufacture of theranostic gold nanoparticles (NPs), which have been generated using various materials. On the other hand, chemically produced nanoparticles have several drawbacks in terms of cost, toxicity, and effectiveness. A plant-mediated integration of metallic nanoparticles has been developed in the field of nanotechnology to overcome the drawbacks of traditional synthesis, such as physical and synthetic strategies. Nanomaterials' tunable features make them sophisticated tools in the biomedical platform, especially for developing new diagnostics and therapeutics for malignancy, neurodegenerative, and other chronic disorders. Therefore, this review outlines the theranostic approach, the different plant materials utilized in theranostic applications, and future directions based on current breakthroughs in these fields.