Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation.

Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.

Antileishmanial Activities of Medicinal Herbs and Phytochemicals In Vitro and In Vivo: An Update for the Years 2015 to 2021.

Leishmaniasis is one of the most neglected tropical diseases that present areal public health problems worldwide. Chemotherapy has several limitations such as toxic side effects, high costs, frequent relapses, the development of resistance, and the requirement for long-term treatment. Effective vaccines or drugs to prevent or cure the disease are not available yet. Therefore, it is important to dissect antileishmanial molecules that present selective efficacy and tolerable safety. Several studies revealed the antileishmanial activity of medicinal plants. Several organic extracts/essential oils and isolated natural compounds have been tested for their antileishmanial activities. Therefore, the aim of this review is to update and summarize the investigations that have been undertaken on the antileishmanial activity of medicinal plants and natural compounds derived, rom plants from January 2015 to December 2021. In this review, 94 plant species distributed in 39 families have been identified with antileishmanial activities. The leaves were the most commonly used plant part (49.5%) followed by stem bark, root, and whole plant (21.9%, 6.6%, and 5.4%, respectively). Other plant parts contributed less (<5%). The activity was reported against amastigotes and/or promastigotes of different species (L. infantum, L. tropica, L. major, L. amazonensis, L. aethiopica, L. donovani, L. braziliensis, L. panamensis, L. guyanensis, and L. mexicana). Most studies (84.2%) were carried out in vitro, and the others (15.8%) were performed in vivo. The IC50 values of 103 plant extracts determined in vitro were in a range of 0.88 µg/mL (polar fraction of dichloromethane extract of Boswellia serrata) to 98 µg/mL (petroleum ether extract of Murraya koenigii). Among the 15 plant extracts studied in vivo, the hydroalcoholic leaf extract of Solanum havanense reduced parasites by 93.6% in cutaneous leishmaniasis. Voacamine extracted from Tabernaemontana divaricata reduced hepatic parasitism by ≈30 times and splenic parasitism by ≈15 times in visceral leishmaniasis. Regarding cytotoxicity, 32.4% of the tested plant extracts against various Leishmania species have a selectivity index higher than 10. For isolated compounds, 49 natural compounds have been reported with anti-Leishmania activities against amastigotes and/or promastigotes of different species (L. infantum, L. major, L. amazonensis, L. donovani and L. braziliensis). The IC50 values were in a range of 0.2 µg/mL (colchicoside against promastigotes of L. major) to 42.4 µg/mL (dehydrodieuginol against promastigotes of L. amazonensis). In conclusion, there are numerous medicinal plants and natural compounds with strong effects (IC50 < 100 µg/mL) against different Leishmania species under in vitro and in vivo conditions with good selectivity indices (SI > 10). These plants and compounds may be promising sources for the development of new drugs against leishmaniasis and should be investigated in randomized clinical trials.

Therapeutic outcomes evaluation of adjuvant hyperbaric oxygen therapy for non-healing diabetic foot ulcers among sudanese patients.

BACKGROUND AND AIMS: Diabetic foot ulcers (DFUs) are common complications of diabetes that frequently lead to amputation and disability. Despite some promising results in using hyperbaric oxygen therapy (HBOT) for DFUs treatment, its efficacy is still debatable. The aim of this study was to evaluate the therapeutic outcomes of adjuvant HBOT in non-healing DFUs treatment. METHODS: A descriptive, retrospective, hospital-based study was conducted at Al-Mo'alem Medical City-Khartoum, Sudan from August to December 2018. Medical records of Type 2 diabetic patients, treated with HBOT plus standard wound care for DFUs, were included in the study. Data were analyzed by simple descriptive statistics and logistic regression. P ≤ 0.05 was considered statistically significant. RESULTS: The study results showed that 51.7% of patients had Wagner grade-3 ulcers and 28.3% had complete loss of protective sensation. Almost 61% of patients achieved complete ulcer healing while 16.7% underwent amputation. Twenty percent of patients treated with HBOT experienced ear barotraumas as adverse effects. Protective sensation (OR = 6.00, 95% CI = 1.79-20.16, p = 0.004) and more sessions of HBOT (OR = 17.35, 95% CI = 4.51-66.73, p = 0.000) were positive predictors of complete ulcer healing. Loss of protective sensation (OR = 0.17, 95% CI = 0.05-0.63, p = 0.007) was an indicator of amputation. CONCLUSIONS: Treatment with adjuvant HBOT enhanced ulcer healing and reduced amputation rate in patients with non-healing DFUs. HBOT could be considered a relatively safe intervention.

In silico assessment of potential leads identified from Bauhinia rufescens Lam. as α-glucosidase and α-amylase inhibitors.

INTRODUCTION: Natural products play a pivotal role in innovative drug discovery by providing structural leads for the development of new therapeutic agents against various diseases.The present study aims to focus on the in silico assessment of the therapeutic potential of antidiabetic phytoconstituents which were identified and isolated from the extracts of Bauhinia rufescens Lam, a medicinal plant traditionally used for various pharmacotherapeutic purposes. METHOD: The physicochemical and pharmacokinetic parameters of the previously isolated thirty eight compounds were predicted using SwissADME web tool whereas OSIRIS Property Explorer was used for toxicity risk assessment and drug- likeliness. Twelve compounds were selected for docking on human α-glucosidase and α-amylaseenzymes using Autodock 4.0 software. Furthermore, the active extract was in vivo tested for the antidiabetic activity and then identified usingTLC bioautographic method. RESULTS AND DISCUSSION: Eriodictyol was found to have the highest potential as an inhibitor against α-amylase with binding energy of -9.92 kcal/mol. Rutin was the most potent against α-glucosidase with binding energy of-9.15 kcal/mol. A considerable number of hydrogen bonds and hydrophobic interactions were computed between the compounds and the enzymes thereby making them energetically favorable and suggesting inhibition of these two enzymes as a plausible molecular mechanism for their antidiabetic effect. CONCLUSION: These two flavonoids could therefore be used as potential leads for structure- based design of new effective hypoglycemic agents.

Isolation and Characterization of Four Terpenoidal Compounds with Potential Antimicrobial Activity from Tarconanthus camphorantus L. (Asteraceae).

OBJECTIVES: The objective of this study is to describe the isolation, characterization, and antimicrobial activity of isolated compounds from Tarconanthus camphorantus. MATERIALS AND METHODS: Bioactive compounds such as trifloculoside, parthenolide (sesquiterpene lactones), lupeol, and erythrodiol (pentacyclic triterpens) were isolated from n-hexane extract of T. camphoratus, and their antimicrobial activity against Candida albicans, Escherichia coli, Psuedomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Mycobacterium smegmatis was evaluated. The compounds were characterized using chromatographic and spectroscopic techniques. RESULTS: Trifloculoside, lupeol, and erythrodiol are being reported for the first time from T. camphoratus. The isolated compounds sesquiterpens and lupeol exhibited prodigious antimicrobial activity against B. subtilis and S. aureus with minimum inhibitory concentration values in the range of 25-1000 µg/mL but no activity was observed against other tested organisms, and erythrodiol showed no antimicrobial activity against any of the tested organisms. CONCLUSION: The findings of this study revealed that the new compounds trifloculoside, parthenolide, and lupeol isolated from T. camphoratus exhibited effective antimicrobial potential. It was inferred that T. camphoratus can be effectively used in traditional medicine.

Effect of some plants' extracts used in Sudanese folkloric medicines on carrageenan-induced inflammation.

Investigations for anti-inflammatory potential and categorization of Sudanese medicinal plants according to their potency. Anti-inflammatory effect of plants' extracts of 17 genera were studied using the carrageenan induced inflammation in rats' paws. The plant extracts were obtained using methanol and dichloromethane as solvent and administered intra peritoneally at the concentration of 2g/kg body weight. The results obtained in this experiment strongly support and validate the traditional uses of these Sudanese medicinal plants to treat various inflammatory diseases. 63.9% of plants extracts showed marked inhibition of inflammation induced by carrageenan (78.3% out of this percentage represented by methanolic extract), 27.8% showed no activity and 8.3% enhanced the carrageenan induced inflammation. The anti-inflammatory effect of many of these plants has not been reported previously, yet they have been extensively used in Sudanese folkloric medicine. The result of this study justify the traditional medicinal use of the evaluated plants species in treating inflammatory disorders and helped in categorizing the investigated plants into most useful, moderately useful and least useful category for inflammatory diseases. Out of the 17 investigated plant species 05 belongs to most useful and 06 belongs to moderately useful category. However, toxicity studies are required to prove the safety of these plant materials.