Green Synthesis and Characterization of Silver Nanoparticles from Eclipta alba and Its Activity Against Triple-Negative Breast Cancer Cell Line (MDA-MB-231).

Triple-negative breast cancer (TNBC) doesn't have well-defined molecular targets making it unable to treat with chemotherapy also have faster metastatic rate and worse survival rate. In the current study we aim to target TNBC through eco-friendly green synthesized silver nanoparticles having anti-cancer phytoconstituents from the traditional anti-cancer medicinal plant Eclipta alba. Green synthesized silver nanoparticles (AgNPs) are agglomerates of spherical shaped 40-60 nm sized showing characteristic light absorption at 437 nm, banding pattern at 1479, 1285, 1036, and 471 showing and further X-ray diffraction pattern confirm face-centered cubic crystal silver structure exist in the green synthesized silver nanoparticle preparation. Further in vitro anti-oxidant analysis results revealed that green synthesized AgNPs showed 2.6-fold higher anti-oxidant potential (IC50 15.70 g/ml) than that of aqueous plant leaf extract (IC50 39.80 g/ml). In MTT cytotoxicity analysis Eclipta alba plant extract and AgNPs both display dose-dependent cytotoxicity against triple-negative breast cancer cells (MDA-MB-231), although their IC50 values differ substantially, at 105.80 µg/ml and 77.20 g/ml, respectively. Finally, AgNPs from Eclipta alba tested for anti-leishmanial activity and it showed 91.36 ± 1.05 for promastigotes and 76.62 ± 0.95 for amastigotes at the highest dose of 400 g/ml. Altogether present data showed that Eclipta alba leaf extract actively bonded with silver nanoparticles suppresses the MDA-MB-231 cells growth through high antioxidant characters and anti-leishmanial activity. From together we confirm that Eclipta alba was recommended to a future therapeutic drug and agent to control breast cancer in the clinical level.

Molecular insight of phytocompounds from Indian spices and its hyaluronic acid conjugates to block SARS-CoV-2 viral entry.

Human corona viral infection leads to acute breathing disease and death if not diagnosed and treated properly in time. The disease can be treated with the help of simple natural compounds, which we use in day-to-day life. These natural compounds act against several diseases but their drug targeting mechanism needs to be improved for more efficient and promising applications. In the present study five compounds (gingerol, thymol, thymohydroquinone, cyclocurcumin, hydrazinocurcumin) from three Indian medicinal plants (ginger, black cumin, turmeric) and its hyaluronic acid (HA) conjugates were docked against initially deposited spike structural proteins (PDB ID 6WPT) and its mutant variant D-614G (PDB ID 6XS6). Docking study result reveals that all the HA conjugates showed the most effective inhibitor of S-protein of initially deposited and D-614G variant forms of SARS-CoV-2. The compounds like Gingerol, Thymol, Thymohydroquinone, Cyclocurcumin, Hydrazinocurcumin, Hydroxychloroquinone, and hyaluronic acid conjugates inhibit the viral protein of both wild-type and mutated S-protein of SARS-CoV-2. The molecular docking studies of phytocompounds with initial deposited and variant spike protein targets show superior binding affinity than with the commercial repurposed viral entry inhibitor hydroxychloroquine. Further, the docking result was modeled using MD simulation study shows excellent simulation trajectories between spike proteins and HA conjugates spices constituents than its free form. DFT analysis was carried out to affirm the reason behind the highest binding affinity of HA conjugates over its free form towards SARS-CoV-2 spike protein targets. Further HA conjugates synthesis and its evaluation against SARS-CoV-2 in vitro studies are needed to prove our novel idea for an anti-viral drug.Communicated by Ramaswamy H. Sarma.

Analgesic and anti-inflammatory potential of Lupeol isolated from Indian traditional medicinal plant Crateva adansonii screened through in vivo and in silico approaches.

BACKGROUND: Lupeol, a triterpene bioactive compound isolated from Indian traditional plant Crateva adansonii acted as promising and alternative anti-inflammatory agent to treatments of diseases related to inflammation. The inflammatory process in the body serves an important function in the control and repair of injury. However, it is self-perpetuating in number of disease conditions, which must be prevented and treated. Worldwide most prescribing NASID drug shows severe side effects. Whereas drug from natural origin shows dual inhibition of inflammatory and analgesic target protein with more efficacy and less side effects than NSAID drugs. Our study aims to isolate and screen the analgesic and anti-inflammatory potential of lupeol, a pentacyclic triterpenoid isolated from leaf extract of Crateva adansonii belongs to Capparaceae family commonly used Indian traditional medicine for treating inflammatory diseases. RESULTS: Methanol and chloroform leaf extracts (ME and CE) and lupeol fraction (LF) of plant Crateva adansonii is investigated through employing in vivo male Wistar albino rat model. Acute toxicity study of C. adansonii ME and CE leaf extracts reveals that no mortality and no behavioral changes in experimental animals up to 2 g/kg. So no lethal dose we consider two optimal doses 200 and 400 mg of plant leaf extracts for in vivo inflammatory and analgesic study. In vivo acute and chronic anti-inflammatory activity was carried out through carrageenan-induced rat paw edema and cotton pellet-induced granuloma models. LF (100 mg/kg, oral route) of Crateva adansonii evoked highest percentage of inflammation inhibition (50 and 33.96% respectively) in both in vivo acute and chronic inflammation model among all tested samples (ME and CE 200 mg and 400 mg/kg, oral route) including reference standard (10 mg/kg, oral route) indomethacin. Carrageenan-challenged experimental animals were screened for one inflammatory marker enzyme myeloperoxidase (MPO), inflammatory products such as Prostaglandrin E2 (PGE2), and eight different cytokines markers (TNFα, IL-6, IFN γ, IL-1α, IL-1ß, MCP-1, Rantes, and MIP) associated with inflammation reveals that LF (100 mg/kg, oral route) of Crateva adansonii shows prominent anti-inflammatory activity than reference standard indomethacin (10 mg/kg, oral route) over all these biological tested parameters. In vivo analgesic assays such as hot plate assay and acetic acid-induced writhing assay revealed that LF (100 mg/kg, oral route) possesses significant analgesic activity (11.60 s and 69.05%) when compared with standard drug pentazocine(10 mg/kg, oral route). Finally, we made an in silico screening of lupeol against analgesic (nAChR) and anti-inflammatory (COX-2) target proteins reveals that lupeol possess highest binding affinity with nAChR and COX-2 target proteins (- 8.5 and - 9.0 Kcal/mol) over the reference standard pentazocine and indomethacin (- 7.0 and - 8.4 Kcal/mol) respectively. CONCLUSION: The present study result provides a pharmacological evidences for analgesic and anti-inflammatory potential of lupeol isolated from Indian traditional plant Crateva adansonii act as a multi-target agent with immense anti-inflammatory potential targeting key molecules of inflammation such as MPO, PGE2, and eight pro-inflammatory cytokine markers. Outcome of present study is to find promising anti-inflammatory bioactive agents from the cheapest Indian traditional medicinal plant sources useful for pharmaceutical industries.

Screening of anti-inflammatory phytocompounds from Crateva adansonii leaf extracts and its validation by in silico modeling.

Anti-inflammatory phytocompounds from Crateva adansonii DC leaf extracts were identified by GCMS analysis and its anti-inflammatory potential was evaluated by in silico molecular docking study against inflammatory molecular targets. Three different (Aqueous, Methanol and Petroleum ether) dried leaf extracts of Crateva adansonii were obtained from soxhlet extraction method. Preliminary phytoconstituents analysis of three different leaf extracts of C. adansonii confirmed the presence of various major classes of bioactive phytoconstituents such as polyphenols (tannins and flavonoids), steroids, alkaloid, coumarin, carbohydrate and terpenoids. Among three leaf extracts, methanolic leaf extract possess highest total phenolic content of 77 ±â€¯1.65 µg gallic acid equivalent (GAE)/g of dry weight of leaf extract, subsequently methanolic leaf extract also shows maximal in vitro antioxidant activity (DPPH scavenging activity) of 71.22 ±â€¯1.32% among three different leaf extracts. GC-MS analysis of petroleum ether leaf extract revealed the presence of nine phytocompounds representing 95.43% peak area percentage, among nine identified phytocompounds three phytocompounds of C. adansonii possess anti-inflammatory property namely phytol, 1-Hexyl-2-Nitrohexane and 2-Isopropyl-5-Methylcyclohexyl 3-(1-(4-Chlorophenyl)-3-Oxobutyl)-Coumarin-4-Yl Carbonate were chosen for in silico molecular docking study against four inflammatory receptor targets (COX-2, TNFα, IL-1ß and IL-6) and they shows less binding energy with highest docking score ranging from -15.9500 to 5.0869. The present study substantially indicated and proven that anti-inflammatory potential of phytocompounds from C. adansonii leaf extracts which can be exploited for commercial designing of novel anti-inflammatory drug to treat various inflammatory disorders.