Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC502–8 μM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC50 range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.

Analgesic activity of Phong Thap Dan tablets in animal models

Phong thap dan tablets are intended to treat low back pain. This study was carried out to evaluate theanalgesic effects of Phong thap dan tablets in experimental animals. The analgesic effects were evaluated inthree animal models: hot plate, mechanical stimulation and acetic acid-induced writhing test. Mice were dividedinto 4 groups given oral water, control drug (codein phosphate in hot plate and mechanical stimulation tests oraspirin in writhing test), Phong thap dan at 2.88 tablets (1.44 g) or 8.64 tablets (4.32 g)/kg b.w/day, respectively.Our results showed that Phong thap dan tablets at both doses increased the reaction time to thermal stimulation,increased the paw withdrawal latency and the force required to elicit a paw withdrawal and decreased thenumber of acetic acid-induced writhing movements in mice. There was no statistically significant differencebetween 2 doses of Phong thap dan tablets in three animal models. We conclude that Phong thap dan tabletsat the doses of 2.88 tablets and 8.64 tablets/kg b.w/day showed significant analgesic effect in animal models.

A Clinical Study of Maltyadi Tail in the Management of Darunak W.R.S. To Dandruff

Darunak is a Vata –Kaphaj Vyadhi. Sushruta mentioned it under Kshudra roga. Chakradatta has mentioned application of Maltyadi Tail (Jaati, Karveer, Chitrak, Karanj, base oil- Tila Tail) in the treatment of Darunak. Aggravation of Kapha and Vata in Darunak causes, itching, falling of hair, loss of sensation, dryness and small cracks of the skin of the scalp. Several factors increase the risk of developing dandruff, including a person’s age, the weather, stress levels, fungus, medical conditions, and choice of hair products. Oiling is the best way to get a healthy scalp. Aim and objective: To evaluate efficacy of Maltyadi Tail in the management of Darunak w.s.r to dandruff. Materials and Methods: In this clinical study total 46 Patients of Darunak were registered out of which 3 patients left the treatment; remaining 43 patients were divided into 2 groups. 23 patients were treated in group A (test drug- Maltyadi Tail) and 20 patients were treated in group B (control drug- Tila Tail) for 30 days. The effect of therapy was assessed on the basis of changes in grading score. Result: In clinical study, All the cardinal and associate symptoms except Raag, Daah, Ruja were statistically significant improved after the complete course of test drug (Maltyadi Tail). Effect of Group A reduced Kesha Bhoomi Rookshta by 92.68%, Kandu by 100%, Keshbhoomi Prapatan by 92.68% and Keshchyuti by 87.50% which was statistically highly significant. Conclusion: The study revealed that test drug (Maltyadi tail) is more effective in Darunak /dandruff compare to control drug (Tila Tail).

Formulation and Characterization of Chitosan Based Dexibuprofen Nanoparticles Using Ionotropic Gelation Method

Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID), which is used to treat pain and inflammation. Like common NSAIDs, Dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. The therapeutic use of Dexibuprofen is limited by the rapidity of the onset of its action and its short biological half-life. Hence, our aim was to develop Dexibuprofen nanoparticles formulation to overcome these disadvantages using optimized concentration of polymers by appropriate methods for nanoparticle preparation. The drug and the nanoparticle formulation of Dexibuprofen F11 were comparatively assessed for FT IR spectrums by using FT-IR method. The DSC study was used as one of the tool to assess the compatibility between drug and the excipients. As per DSC thermograms, the drug as well as drug with mixture of excipients chitosan, sodium tripolyphosphate had shown no interactions with dexibuprofen. The ionotropic gelation method was used to prepare Dexibuprofen nanoparticles. The chitosan and sodium tripolyphosphate (TPP) of different concentrations were used as polymers to prepare Dexibuprofen nanoparticles. Total eleven different formulations were explored with different concentrations of drug : polymer ratios using ionotropic gelation method to identify optimal concentrations of polymer. Among different formulations, F11 formulation with optimized concentration of 5% chitosan and 1% Sodium tripolyphosphate polymers along with Dexibuprofen showed maximum drug release. The objective was to evaluate the developed Dexibuprofen nanoparticles. In-vitro drug release was evaluated in 0.05M phosphate buffer pH7.2 and found that the drug release of F11 formulation of Dexibuprofen nanoparticle had shown release till 24 hours more than that of other trials. Hence, F11 formulation was considered as the optimized nanoparticle formulation to control drug release till 24 hours. The entrapment efficacy of the formulated Nanoparticles was found to be in the range of 75.48%-91.22% respectively.

ANTI-PYRETIC AND ANTI-INFLAMMATORY ACTIVITY OF AQUEOUS EXTRACT OFSOLANUM XANTHOCARPUM BERRIES IN SUITABLE ANIMAL MODELS

Background: Use of traditional medicines for treating various diseases have become a topic of global importance because of their safety, less side effects and cost-effectiveness. The present study was undertaken to evaluate the anti-pyretic and anti-inflammatory activity of aqueous extract of Solanum xanthocarpum berries (SXB) in suitable animal models. Methods: Anti-pyretic activity was assessed by dried yeast induced pyrexia in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw oedema in rats. Three doses of the plant extract (500, 1000 and 1500 mg/kg) prepared by dissolving the drugs in 2% gum acacia were used. Paracetamol 33 mg/kg and aspirin 100 mg/kg were used as standard drugs for anti-pyretic and anti-inflammatory activity respectively. Vehicle served as a control drug. Results: Acute toxicity study results demonstrated no mortality of animals after 24 hours. The aqueous extract of the plant significantly decreased the rectal temperature of the rats and significantly prevented increase in volume of paw oedema. Conclusion: The aqueous extract of Solanum xanthocarpum berries exerts its anti-pyretic and anti-inflammatory activity activity. However, further studies with the plant are required to evaluate the dose dependent activity and also to determine the active principle responsible for exact mechanism for both antipyretic and anti-inflammatory activity.

Formulation and Evaluation of colon targeted drug Delivery of Diloxanide furoate Tablets using pH Dependent Polymers

Diloxanide Furoate is a Dichloroacetamide derivative utilized for the treatment of various protozoal infections like amoebiasis. Colon targeted tablets were designed using pH sensitive polymers like Eudragit S100, Eudragit L 100,Cellulose acetate phthallate at different concentrations. All the matrix,compression coated formulations showed the desired physicochemical properties as per the official limits. The drug release studies were performed according to the USP paddle method by using 0.1N HCL for 2 hours, pH 7.4 phosphate buffer for 3 hours and pH 6.8 phosphate buffer upto 18 hours. A better controlled drug release was shown for Eudragit L 100. Based on the comparative drug release studies among different Formulations F9 with Eudragit L 100 polymer showed better control drug release. The release kinetics for the Optimised Formulation F9 was calculated and “r2” value was more for Zero order kinetics i.e.,0.970 indicating that the formulation doesnot depend upon its concentration and from the Korsmeyer peppas model the diffusion exponent value “n” is > 1 indicating that it follows super case II transport mechanism. The accelerated stability studies conducted for optimised formulation F9 for 3 months have no significant variation.

Phytochemical and Antimicrobial Screening of Leaf and Tuber Extracts of Tephrosia calophylla Bedd

Tephrosia calophylla, (Fabaceae) a perennial woody under shrub endemic to south India. It is one of 13 rare or threatened Tephrosia species. Commonly it is known as Adavivempali. The various species of Tephrosia is ascribed to have many medicinal and therapeutic uses. The importance of this study was to preliminary screening of different phytochemical constituents for the detection of various secondary metabolites and evaluation of antibacterial, antifungal activity and Minimum Inhibitory Concentration of the different crude extracts of tuber and leaf. Tuber and leaf both yielded more number of secondary metabolites like alkaloids, phenols, flavonoids tannins, saponins and glycosides with high quantity when compared with the leaf, consisting low quantities of phyto-constituents as steroids and in tuber consisting only tannins. Antibacterial activity of T. calophylla tuber and leaf aqueous and alcohol extracts at 10 mg/well are showing more effective activity on Bacillus subtilis (MTCC-441), Escherichia coli (MTCC-443), Pseudomonas aeruginosa (MTCC-741), Klebsealla neumoniae, Proteus vulgaris strains than the control drug Ampicillin 10 mg/well with 30.25-15.00 mm zone of inhibition. The minimum inhibitory concentration (MIC) with leaf and tuber extracts was 0.312 to 2.50 mg/ml compared to that of the 10 mg of Ampicillin. Antifungal screening of aqueous leaf extract was more effective on Candida albicans with 19.25 mm inhibition zone than Aspergillus niger at 10 mg/well compared to Nystatin the control drug at 10 mg/well with 10.2 to 12.1 mm of zone of inhibition. Fungal MIC on both organisms with leaf and tuber extracts ranges from 0.612 mg to 3 mg compared to 10 mg of Nystatin.

Phytochemical-Based Nano-Pharmacotherapeutics for Management of Burn Wound Healing

Medicinal plants have been used since ancient times for their various therapeutic activities and are safer compared to modern medicines, especially when properly identifying and preparing them and choosing an adequate dose administration. The phytochemical compounds present in plants are progressively yielding evidence in modern drug delivery systems by treating various diseases like cancers, coronary heart disease, diabetes, high blood pressure, inflammation, microbial, viral and parasitic infections, psychotic diseases, spasmodic conditions, ulcers, etc. The phytochemical requires a rational approach to deliver the compounds to enhance the efficacy and to improve patients’ compatibility. Nanotechnology is emerging as one of the most promising strategies in disease control. Nano-formulations could target certain parts of the body and control drug release. Different studies report that phytochemical-loaded nano-formulations have been tested successfully both in vitro and in vivo for healing of skin wounds. The use of nano systems as drug carriers may reduce the toxicity and enhance the bioavailability of the incorporated drug. In this review, we focus on various nano-phytomedicines that have been used in treating skin burn wounds, and how both nanotechnology and phytochemicals are effective for treating skin burns.