Appraising the therapeutical potentials of Alchornea laxiflora (Benth.) Pax & K. Hoffm., an underexplored medicinal herb: A systematic review

Ethnopharmacological relevance:Alchornea laxiflora (Benth.) Pax & K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy.Material and methods: The scientific name of the plant was validated using the “The Plant List,” “Kew Royal Botanic Gardens,” and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley.Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively.Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression

Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis.Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID. Essential bioactive compounds, potential targets, and signaling pathways were predicted using in silico analysis, including BA-TAR, PPI, BA-TAR-PATH network construction, and GO and KEGG pathway enrichment analysis. Later on, with molecular docking analysis, the interaction of essential bioactive compounds of A. laxiflora and predicted core targets of depression were verified.Results: The network pharmacology approach identified 15 active compounds, a total of 219 compound-related targets, and 14,574 depression-related targets with 200 intersecting targets between them. SRC, EGFR, PIK3R1, AKT1, and MAPK1 were the core targets, whereas 3-acetyloleanolic acid and 3-acetylursolic acid were the most active compounds of A. laxiflora with anti-depressant potential. GO functional enrichment analysis revealed 129 GO terms, including 82 biological processes, 14 cellular components, and 34 molecular function terms. KEGG pathway enrichment analysis yielded significantly enriched 108 signaling pathways. Out of them, PI3K-Akt and MAPK signaling pathways might have a key role in treating depression. Molecular docking analysis results exhibited that core targets of depression, such as SRC, EGFR, PIK3R1, AKT1, and MAPK1, bind stably with the analyzed bioactive compounds of A. laxiflora.Conclusion: The present study elucidates the bioactive compounds, potential targets, and pertinent mechanism of action of A. laxiflora in treating depression. A. laxiflora might exert an antidepressant effect by regulating PI3K-Akt and MAPK signaling pathways. However, further investigations are required to validate

Discovery of novel N-methyl carbazole tethered rhodanine derivatives asdirect inhibitors ofMycobacterium tuberculosisInhA

International audienc

Mucilage of Coccinia grandis as an Efficient Natural Polymer-Based Pharmaceutical Excipient

Natural eco-friendly materials are recently employed in products to replace synthetic materials due to their superior benefits in preserving the environment. The herb Coccinia grandis is widely distributed in continents like Asia and Africa and used traditionally to treat fever, leprosy, asthma, jaundice, and bronchitis. Mucilage of Coccinia grandis was accordingly extracted, isolated by a maceration technique, and precipitated. The mucilage was evaluated for its physicochemical, binding, and disintegrant properties in tablets using paracetamol as a model drug. The crucial physicochemical properties such as flow properties, solubility, swelling index, loss on drying, viscosity, pH, microbial load, cytotoxicity was evaluated and the compatibility was analyzed using sophisticated instrumental methods (TGA, DTA, DSC, and FTIR). The binding properties of the mucilage was used at three different concentrations and compared with starch and PVP as examples of standard binders. The disintegrant properties of mucilage were used at two different concentrations and compared with standard disintegrants MCCP, SSG, and CCS. The tablets were punched and evaluated for their hardness, friability, assay, disintegration time, in vitro dissolution profiles. In vitro cytotoxicity studies of the mucilage were performed in a human embryonic kidney (HEK) cell line. The outcome of the study indicated that the mucilage had good performance compared with starch and PVP. Further, the mucilage acts as a better disintegrant than MCCP, SSG and CCS for paracetamol tablets. Use of a concentration of 3% or less demonstrated the ability of the mucilage to act as a super disintegrating agent and showed faster disintegration and dissolution, which makes it as an attractive, promising disintegrant in formulating solid dosage forms to improve the therapeutic efficacy and patient compliance. Moreover, the in vitro cytotoxicity evaluation results demonstrated that the mucilage is non-cytotoxic to human cells and is safe

Crystal structure of the Eg5 - K858 complex and implications for structure-based design of thiadiazole-containing inhibitors

The thiadiazole scaffold is an important core moiety in a variety of clinical drug candidates targeting a range of diseases. For example, the 2,4,5-substituted 1,3,4-thiadiazole scaffold is present in a lead compound and at least two clinical candidates targeting the human motor protein Eg5, against neoplastic diseases. An inhibitor named K858 has in vivo activity in various mouse xenografts whereas the clinical candidates (S)-ARRY-520 and (R)-Litronesib have entered clinical trials with the former one in phase III clinical trials either alone or in combination with a proteasome inhibitor against relapsed/refractory multiple myeloma. Astonishingly, structural data are lacking for all thiadiazole-containing Eg5 inhibitors. Here we report the structure determination of two crystal forms of the ternary Eg5-ADP-K858 complex, locking the motor in the so-called final inhibitor bound state, thus blocking ADP release, a crucial stage for Eg5 activity. K858 acts at the established allosteric inhibitor-binding pocket formed of helix α2, loop L5 and helix α3. The structure of the complex has far reaching consequences for thiadiazole containing Eg5 inhibitors. For example, we could rationalise the structure-activity relationship in the crucial 5-position of the thiadiazole scaffold and the complex will serve in the future as a basis for strucutre-based drug design

Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents

A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N4 piperazine was found to be the most active with the promising IC50 (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery

Development and Characterization of Gel-Based Buccoadhesive Bilayer Formulation of Nifedipine

A promising controlled drug delivery system has been developed based on polymeric buccoadhesive bilayered formulation that uses a drug-free backing layer and a polymeric hydrophilic gel buccoadhesive core layer containing nifedipine. The DSC thermogravimetric analysis confirms the drug’s entrapment in the gel layer and reveals no evidence of a potential interaction. Various ratios of bioadhesive polymers, including HPMC K100, PVP K30, SCMC, and CP 934, were combined with EC as an impermeable backing layer to ensure unidirectional drug release towards the buccal mucosa. The polymeric compositions of hydrophilic gel-natured HPMC, SCMC, and CP formed a matrix layer by surrounding the core nifedipine during compression. Preformulation studies were performed for all of the ingredients in order to evaluate their physical and flow characteristics. Ex vivo buccoadhesive strength, surface pH, swelling index, in vitro and in vivo drug release, and ex vivo permeation investigations were performed to evaluate the produced gel-based system. Rapid temperature variations had no appreciable impact on the substance’s physical properties, pharmacological content, or buccoadhesive strength during stability testing using actual human saliva. It was clear from a histological examination of the ex vivo mucosa that the developed system did not cause any irritation or inflammation at the site of administration. The formulation NT5 was the best one, with a correlation coefficient of 0.9966. The in vitro and in vivo drug release profiles were well correlated, and they mimic the in vitro drug release pattern via the biological membrane. Thus, the developed gel-based formulation was found to be novel, stable, and useful for the targeted delivery of nifedipine

Development of a Polyherbal Topical Gel for the Treatment of Acne

The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of the skin. Aloe barbadensis pulp was collected and mixed with the extract of Vigna radiata and formulated into a gel using Carbopol 940, triethanolamine, and propylene glycol as the gelling agent, viscosity modifier, and pH modifier, respectively. The gel was evaluated for its antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans. Antimicrobial agents, such as gentamycin and fluconazole, were used as the standards. The developed formulation showed promising zone of inhibition. The gel was further evaluated for its physicochemical properties. The formulation showed a promising effect on acne together with the additive effect of Aloe barbadensis on skin

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. <i>In vitro</i> antimycobacterial activity of synthesized compounds was evaluated against <i>Mycobacterium tuberculosis</i> H₃₇Rv strain. Among the series, compound <b>6o</b> exhibited significant activity (MIC = 1.5 μM; IC₅₀ = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC₅₀ = <0.098 μM). Furthermore, <b>6o</b> displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents