Development of Daruharidra (Berberis aristata) Based Biogenic Cadmium Sulfide Nanoparticles: Their Implementation as Antibacterial and Novel Therapeutic Agents against Human Breast and Ovarian Cancer.

BACKGROUND: This article presents a new and environmentally friendly method for generating DH-CdSNPs (cadmium sulfide nanoparticles) ranging from 5-10 nm in size. A green synthesis method for the development of inorganic nanoparticles was developed a few years back for their applications in diverse fields, such as medicine, bioimaging and remediation. The biogenic synthesis of these nanoparticles containing daruharidra (Berberis aristata) and cadmium sulfide is an effective alternative. AIMS: By employing Daruharidra extract as a herbal analog, we aim to minimize the risks and adverse effects that come along with the use of other chemically synthesized nanoparticles. This study's main goal was to investigate the potential of these nanoparticles as powerful antibacterial and anticancer agents. METHODS: We used a crude powdered daruharidra extract as a stabilizer ingredient to create CdSbased nanoformulations in an environmentally responsible way. By exposing the breast cancer cell line (MDAMB-231) and ovarian teratocarcinoma cell line (PA1) to these nanoformulations, we were able to evaluate their anticancer activities. Additionally, flow cytometry analysis was conducted to scrutinize the process of cell cycle arrest and apoptosis in reference to anticancer studies. Furthermore, DH-CdSNPs were applied on different gram-positive as well as gramnegative bacteria in a disc diffusion assay to ascertain their antibacterial activity. Nanoparticles were tested on bacterial strains to check if they were resistant after the MIC or minimum inhibitory concentration. RESULTS: The cytotoxicity of nanoparticles was tested by MTT assay. The impact of increasing concentrations of NPs on cell lines was tested, revealing a cytotoxic effect. The half-maximal inhibitory concentration values for a 24-hour treatment were determined to be 95.74µg/ml for ovarian cancer cells and 796.25 µg/ml for breast cancer cells. Treatment with DH-CdSNP resulted in a noteworthy increase in early apoptotic cells, with percentages rising from approximately 3% to 14.5% in ovarian cancer cell lines and from 4% to 13.6% in breast cancer cell lines. Furthermore, the NPs induced arrest of the cell cycle, specifically in the interphase of G2 and mitosis phase, with DNA damage observed in sub G1 in ovarian cancer cells and G0/G1 arrest observed in breast cancer cells. Additionally, the NPs exhibited exceptional potency against both gram-positive as well as gram-negative bacteria. CONCLUSION: Less research has been done on using bioinspired DH-CdSNP to deliver anticancer medications. The amalgamation of plant extract and the DH-CdSNP could cause a paradigm shift in the cancer therapy approach. The findings revealed that the biosynthesized DH-CdSNP limited the growth of human breast and ovarian cancer cells. This property can be further investigated against a variety of additional cell lines to determine whether this property makes the DH-CdSNP a promising treatment alternative. The results obtained from these nanoformulations exhibit faster efficacy compared to traditional medications.

A comprehensive review on ayurvedic herb Leptadenia reticulata (Jeevanti): a phytochemistry and pharmacological perspective.

Leptadenia reticulata is a vital Ayurvedic medicinal herb, commonly known as Jivanti or Jiv, and contains revitalising, rejuvenating, and lactogenic activities. It has been used in traditional medicine for treating respiratory disorders, wounds, inflammation, cough, dehydration, tuberculosis, colitis, chickenpox, dysentery, eye diseases, night blindness, fever, and snake bites. It is a perennial herb of Indian origin belonging to the Asclepiadaceae family and has been utilised for its therapeutic properties since ancient times. It is a key ingredient in several marketed herbal drugs, including chyawanprash, speman, and leptaden. Several potent compounds, including ß-sitosterol, γ-sitosterol, phytol, α-amyrin, ß-amyrin, apigenin, reticulin, deniculatin, leptaculatin, diosmetin, and rutin are present in this herb and attributed various pharmacological activities, including antidiabetic, antimicrobial, antioxidant, anti-abortifacient, anticancer, antipyretic, analgesic, anti-inflammatory, and antiulcer properties. This review provides an in-depth analysis of the distribution, ethnobotanical use, botanical description, phytocompounds, and pharmacological activities of Leptadenia reticulata.

Leptadenia reticulata is a vital Ayurvedic herb containing revitalising, rejuvenating, and lactogenic activities.It is present in polyherbal formulations chyawanprash, speman, and leptaden.Its secondary metabolites have anticancer, anticholesterol, antidiabetic, antiabortifacient, and anti-inflammatory potential.This review shows the distribution, morphology, and therapeutic potential of Leptadenia reticulata.A summary of the phytochemicals present in Leptadenia reticulata will also be provided.

Exploring plant-based alpha-glucosidase inhibitors: promising contenders for combatting type-2 diabetes.

Objective: This systematic review aimed to provide comprehensive details on the α-G inhibitory potential of various bioactive compounds derived from natural sources.Methods: A comprehensive literature search was conducted using various databases and search engines, including Science Direct, Google Scholar, SciFinder, Web of Science, and PubMed until May, 2023.Results and conclusions: The enzyme alpha-glucosidase (α-G) is found in the brush border epithelium of the small intestine and consists of duplicated glycoside hydrolase (GH31) domain. It involves the conversion of disaccharides and oligosaccharides into monosaccharides by acting on alpha (1 → 4) and (1 → 6) linked glucose residue. Once absorbed, glucose enters the bloodstream and elevates postprandial glucose, which is associated with the development of type 2 Diabetes (T2D). Epidemic obesity, cardiovascular disease, and nephropathy are linked to T2D. Traditional medicinal plants with α-G inhibitory potential are commonly used to treat T2D due to the adverse effects of currently used α-G inhibitors miglitol, acarbose, and voglibose. Various bioactive compounds derived from natural sources, including lupenone, Wilforlide A, Baicalein, Betulinic acid, Ursolic acid, Oleanolic acid, Katononic acid, Carnosol, Hypericin, Astilbin, lupeol, betulonic acid, Fagomine, Lactucaxanthin, Erythritol, GP90-1B, Procyanidins, Galangin, and vomifoliol retain α-G inhibitory potential for regulating hyperglycaemia.

HR-LCMS and evaluation of anti-diabetic activity of Hemidesmus indicus (anantmool): Kinetic study, and molecular modelling approach.

This study delved into the exploration of novel antidiabetic medications acquired from natural resources, utilizing the Ayurvedic Rasayana herb Hemidesmus indicus through cutting-edge chemoprofiling and molecular modelling techniques. The methanolic extract of Hemidesmus indicus root exhibited the highest extractive yield (24.70 ± 0.08 %) and contained substantial levels of total phenolic and flavonoid content as 154.15 ± 1.24 mg Gallic Acid Equivalent/g extract and 70.61 ± 0.35 Quercetin Equivalent/g extract respectively. Invitro study revealed the potent inhibitory potential of methanolic extract of the herb against essential carbohydrate hydrolytic enzymes α-amylase (IC50 = 4.19 ± 0.04 mg/ml) and α-glucosidase (IC50 = 5.78 ± 0.10 mg/ml). Further, the enzyme kinetic study demonstrated the competitive mode of inhibition of both enzymes. HR-LCMS analysis identified the major phytoconstituents present in the extracts, including Solanocapsine, Cyclovirobuxine C, Lucidine B, Zygadenine, Aspidospermidine, silychristin, 3beta-3-Hydroxy-18-lupen-21-one, Manglupenone, and 19-Noretiocholanolone. Molecular docking, molecular dynamic simulation, and MM/GBSA analysis have proved stable, rigid, compact, and folded form of complexes during the entire 100 ns simulation, illustrating Zygadenine, Solanocapsine, and Cyclovirobuxine C as the superior inhibitors of α-A protein, while Zygadenine, Plumieride, and Phlegmarine exhibited greater inhibitory behaviour towards α-G protein than the FDA-approved drug acarbose. Collectively, our findings indicate that the Hemidesmus indicus could be a promising source of α-A and α-G inhibitors, potentially serving as a lead in order to develop medications for type-2 diabetes.

Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach.

EGFR (epidermal growth factor receptor), a surface protein on the cell, belongs to the tyrosine kinase family, responsible for cell growth and proliferation. Overexpression or mutation in the EGFR gene leads to various types of cancer, i.e., non-small cell lung cancer, breast, and pancreatic cancer. Bioactive molecules identified in this genre were also an essential source of encouragement for researchers who accomplished the design and synthesis of novel compounds with anticancer properties. World Health Organization (WHO) report states that antibiotic resistance is one of the most severe risks to global well-being, food safety, and development. The world needs to take steps to lessen this danger, such as developing new antibiotics and regulating their use. In this study, 6524 compounds derived from Streptomyces sp. were subjected to drug-likeness filters, molecular docking, and molecular dynamic simulation for 1000 ns to find new triple mutant EGFRCSTMLR (EGFR-L858R/T790M/C797S) inhibitors. Docking outcomes revealed that five compounds showed better binding affinity (- 9.074 to - 9.3 kcal/mol) than both reference drug CH7233163 (- 6.11 kcal/mol) and co-crystallized ligand Osimertinib (- 8.07 kcal/mol). Further, molecular dynamic simulation confirmed that ligand C_42 exhibited the best interaction at the active site of EGFR protein and comprised a better average radius of gyration (3.87 Å) and average SASA (Solvent Accessible Surface Area) (82.91 Å2) value than co-crystallized ligand (4.49 Å, 222.38 Å2). Additionally, its average RMSD (Root Mean Square Deviation) (3.25 Å) and RMSF (Root Mean Square Fluctuation) (1.54 Å) values were highly similar to co-crystallized ligand (3.07 Å, 1.54 Å). Compared to the reference ligand, it also demonstrated conserved H-bond interactions with the residues MET_793 and GLN_791 with strong interaction probability. In conclusion, we have found a potential drug with no violation of the rule of three, Lipinski's rule of five, and 26 other vital parameters having great potential in medicinal and pharmaceutical industries applications and can overcome synthetic drug issues.

Molecular modelling and in vitro studies of Daruharidra as a potent alpha-amylase inhibitor.

The present study aims at exploring the potential of the Daruharidra plant (stem and bark) for inhibition of alpha-amylase. Aqueous and ethanolic extraction yielded the highest total phenolic content (TPC) of 101.4 and 111.8 mcg of gallic acid equivalent. Methanol and ethanol extract had Total flavonoid content (TFC) of 319.6 and 288.3 mcg of quercetin equivalent, respectively. In contrast, petroleum ether extraction resulted in the lowest TPC of 23.6 and TFC of 8.33 mcg, respectively. Methanol (5.554 mg/ml), acetone (6.576 mg/ml), and ethanol (7.321 mg/ml) extract had the lowest IC50 values in alpha-amylase inhibition with the mode of inhibition being non-competitive inhibition. HR-LCMS was used for comprehension of phytoconstituents present in the extract. Amongst hundreds of hits observed 10 ligands of alkaloid nature were used for docking studies. Berbamine, alloxanthine, protopine and benazepril along with reference molecule (Acarbose) were subjected to Molecular dynamics (MD) simulation to analyze the stability of the docked protein-ligand complex. The values of RMSD, RMSF, RG, H-Bond and SASA, the interaction energy of all protein-ligand complexes were calculated after 150 ns of MD simulation. The results of screened complexes revealed good stability as compared to reference Acarbose. These screened ligands used for simulation have the most negative binding energies that interacted with alpha amylase enzyme having -9.28 kcal/mol, -7.51 kcal/mol, -7.73 kcal/mol and -8.00 kcal/mol, energies respectively. The results show significant alpha-amylase inhibitory activity and interaction of ligands targeting this enzyme, which can be used for cross-validation, in vitroCommunicated by Ramaswamy H. Sarma.

Alpha-amylase inhibitors from mycelium of an oyster mushroom.

The α-Amylase and α-glucosidase are two main enzymes involved in carbohydrate metabolism. This study was aimed at detecting alpha-amylase inhibitory activity from edible mushroom mycelia. Oyster mushroom was collected from a natural source, from Indian Institute of Technology (Banaras Hindu University) campus and was maintained in vitro in mycelial form. Chloroform, acetone, methanol, and water were used separately for extraction of an active constituent from mycelial cells grown, for 7 days, in potato dextrose broth. The extracts were tested for alpha-amylase inhibitory activity. Chloroform, acetone, and methanol extracts were found to have alpha-amylase inhibitory activity, with IC50 values of 1.71, 224, and 383 µg/mL, respectively. Aqueous extract had no enzyme inhibitory activity. The acetone extract inhibited α-amylase non-competitively whereas chloroform extract showed competitive inhibition. Acetone extraction yielded highest total phenolic content (TPC) of 0.524 mM of gallic acid equivalent, whereas chloroform extraction resulted in lowest TPC of 0.006 mM. The HPLC and absorbance maxima of acetone and chloroform extracts suggest that the bioactive component responsible for enzyme inhibition could be glycoproteins in chloroform extract and catechins (flavonoids) in acetone extract. Thus, the mushroom mycelia under study may be exploited for production and purification of a lead compound for the development of the α-amylase inhibitory drug.

Coronoid process and residual ankylotic mass as an autograft in the management of ankylosis of the temporomandibular joint in young adolescent patients: a retrospective clinical investigation.

The aim of this non-randomised investigation was to assess the feasibility of using autogenous grafts (such as coronoid process and the resected ankylotic mass) in reconstruction of the condyle after gap arthroplasty for ankylosis of the temporomandibular joint (TMJ). Sixteen patients (23 joints) operated on between 2007 and 2009 were studied and postoperative measurements of maximum interincisal opening, bite force, range of movement, and infection were recorded. After a mean (SD) follow up of 55 (2.25) months mouth opening improved from 3 (3.84) mm to 33 (1.66) mm in patients treated with coronoid graft, while in patients treated with an ankylotic mass after a mean (SD) follow up of 58 (1.58) months it increased from 4 (2.64) mm to 26 (8.04) mm. Bite force six months postoperatively ranged from 18.25kg/cm(2) - 27.5kg/cm(2) after reconstruction with the coronoid process and 18.5kg/cm(2) - 23.25kg/cm(2) after reconstruction with the ankylotic mass. One patient developed reankylosis postoperatively and another developed infection, in both of which the ankylotic mass had been used. Both were managed successfully. Both the ankylotic mass and the coronoid process gave satisfactory results and seem to be options for reconstruction. However, the coronoid process graft was better than residual ankylotic mass in terms of masticatory efficiency, bite force, and range of movement.

Comparative analysis of osteosynthesis of mandibular anterior fractures following open reduction using 'stainless steel lag screws and mini plates'.

INTRODUCTION: The purpose of this study was to compare the outcome of open treatment of mandibular fracture (symphysis or parasymphysis) using lag screw or mini plate clinically as well as radiologically in young (age range 12-45 years) and healthy individuals of poor socioeconomic status. METHOD: This prospective study was conducted on 30 patients diagnosed as cases of displaced mandibular anterior fractures treated with open reduction and internal fixation. The patients were then randomly allocated to either of two groups--Group A: Two 2.5 mm stainless steel lag screws were placed in 15 patients. Group B: Two 2.5 mm stainless steel mini plates were placed in 15 patients for the fixation of fractures. Subsequent follow up was done on 2nd, 4th, 6th and 8th week postoperatively. During every follow up patient was assessed clinically for infection, malocclusion, loosening of plate/screw, sensory disturbance, plate fracture, malunion/non-union, devitalisation of associated dentoalveolar segment and masticatory efficiency. Radiographs were taken if necessary and patients were further assessed for any complaint. Pain was objectively measured using a visual analogue scale, bite force was measured using a bite force transducer at biweekly interval. The data collected was subjected to unpaired t test and paired t test for statistical analysis. RESULTS: During follow up period a significant improvement in bite force was present in both the groups, with more improvement seen in the lag screw group (p < 0.01). There was a significant pain reduction present in the lag screw group (p < 0.01) and also masticatory efficiency showed a steadier improvement in lag screw group while mini plate group patients showed a tendency to masticate only food items of medium hard consistency. CONCLUSION: The sample size is small to conclude lag screws are better than mini plates but the result of our study provides a basis for further studies done to conclude that the application of LAG SCREW is an effective, inexpensive, quick treatment modality to accelerate healing of fresh, displaced mandibular anterior fracture.