Revista Brasileira de Farmacognosia

Antimicrobial resistance is emerging as a global health challenge that requires immediate and concerted attention. Accordingly, the WHO has issued alerts urging to continue developing antibiotics with novel mechanisms of action toward clinically important pathogens, including Acinetobacter baumannii. In this context, fungi have played a crucial role in the discovery and development of antibiotics. Therefore, in this work, three fungal strains were prioritized based on their metabolic profiles and antibacterial activity against a pan-resistant isolate of A. baumannii, to identify potential antibiotic molecules. Chemical investigation of the selected fungi (mangrove endophytes) led to the isolation of asperazine (1), aurasperone B (2), aurasperone F (3), TMC-256A1 (4), fonsecin B (5), dianhydroaurasperone C (6), aurasperone A (7), pyrophen (8), and penicillide (9). Moreover, an in vitro assay to detect ligands of the filamentous temperature-sensitive mutant Z enzyme of A. baumannii (AbFtsZ), a GTPase that plays a central role in bacterial division, was developed to correlate the antibacterial properties of the isolated molecules to a mechanism of action. Compounds 1–4 and 9 inhibited the growth of A. baumannii. Interestingly, compounds 2, 3, and 5–9 interacted with AbFtsZ1-412, increasing its GTPase activity. Conversely, compound 4 exhibited an outstanding ability to act as an inhibitor of both the enzymatic activity and the growth of the strain under study.

Schistosomiasis, a neglected tropical disease, affects millions of lives and accounts for thousands of deaths each year. The Schistosoma parasites depend on two hosts during their lifecycle: snails as intermediate hosts and human beings as definitive hosts. Therefore, to control and ultimately eliminate schistosomiasis relies on the reduction of snail populations as well as the prevention and treatment of schistosomiasis infections. Praziquantel is the primary drug for prevention and treatment, and although it is considered safe and efficacious, concerns exist regarding emerging drug resistance due to mass drug administration. For this reason, novel antischistosomal drugs are in need and the genus Artemisia might be a promising source. Notably, Artemisia species not only have been evaluated for their antischistosomal effects against Schistosoma parasites, but also for their molluscicidal effects against the snail vectors. Extracts of Artemisia afra seem to be the most active, with IC50 values comparable with the positive control, praziquantel. The antimalarial drug artemisinin, obtained from A. annua, and its semisynthetic derivatives artemether, artesunate, and artemisone have also been evaluated against both schistosomes and snail vectors. Artemether and artesunate have been found to be notably active against the adult and juvenile stages of schistosomes, whereas artemisone was shown to be effective in treating hosts harboring juvenile schistosomes. Artemisinin on the other hand in combination with praziquantel presents as a good lead combination in curing schistosomiasis.

Gentamicin induced renal complications are well known in humans and animals. Medicinal properties of Withania somnifera (L.) Dunal, Solanaceae, are recognized to improve renal functions. However, the pharmacological function of W. somnifera is not completely understood. We sought to unravel medicinal therapeutic function of W. somnifera on gentamicin-induced nephrotoxicity in wistar rats. Twenty-four adult male wistar rats evenly divided into four groups to evaluate in vivo nephroprotective and nephrocurative function of W. somnifera in gentamicin induced nephrotoxic rats. Experimental design as follows: Group I, saline control for 21 days; Group II, gentamicin nephrotoxic control for eight days; Group III, alcoholic extract of W. somnifera for 13 days + simultaneous administration of gentamicin and W. somnifera, from day 14 to 21 (nephroprotective) and Group IV, gentamicin for 8 days + alcoholic extract of W. somnifera from day 9 to 21 (nephrocurative). End of experiment, respective serum and kidney tissue samples used to analyze renal function. Withania somnifera as a nephroprotective and nephrocurative molecule significantly restore the renal function on gentamicin-induced nephrotoxicity. This phenomenon is accompanied with significantly reduced blood urea nitrogen, creatine, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein, calcium, potassium and kidney malon-dialdehyde concentrations. Additionally, W. somnifera significantly increased antioxidant activities of glutathione and superoxide dismutase to protect renal tissue damage from gentamicin in wistar rats. Over all, W. somnifera treated nephroprotective animal shows improved recovery compared to nephrocuartive. The nephroprotective or nephrocurative effect of W. somnifera could be due to inherent antioxidant and free-radical-scavenging principle(s). In the near future, biologically active compounds of W. somnifera (withanolides) could appear as a novel therapeutic molecule for renal disorders.

Diabetes mellitus is a chronic metabolic disease with a high global incidence that can lead to serious and life-threatening conditions. Diabetes mellitus and its related complications are associated with several inflammatory events majorly caused by irregular insulin action. Toll-like receptors are considered to play a pivotal role in this scenario by acting as a mediator of the immune and inflammatory systems and are part of the innate immunity system recognizing pathogens entering the body, categorized as surface or inner receptors. Different toll-like receptors have been identified and each can further activate other inflammatory pathways. They are believed to be responsible for various inflammatory and immune-related disorders such as rheumatoid arthritis, lupus, and sclerosis. Toll-like receptors are capable of activating nuclear factor kappa B and interferons. Cinnamon as a traditional spice has innumerable health benefits due to its characteristics such as antioxidant, anti-inflammatory, anti-microbial, neuroprotective, lipid-lowering, glucose-lowering, and immunomodulatory. It is considered to be advantageous for diabetic patients and can affect the toll-like receptor pathway. Barks of Cinnamomum species, Lauraceae, are rich in aromatic volatile compounds, such as cinnamaldehyde and cinnamic acid; also no serious side effects have been reported for these compounds. In this review, it was examined how cinnamon could impact diabetes and its complications by affecting the toll-like receptor pathways. Cinnamon derivatives can affect toll-like receptor downstream pathways and cytokines such as NF-κB, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.

Carbamazepine is a first-choice anticonvulsant, and its medication is typically well tolerated when compared to lithium and valproic acid. Patients of Alzheimer’s Disease who are administered carbamazepine tend to develop acute tubulointerstitial nephritis. In this study, we established an Alzheimer’s model using scopolamine in Sprague Dawley rats to find out the nephroprotective effect of matricin (a bioactive sesquiterpene isolated from chamomile flowers) against carbamazepine-induced acute tubulointerstitial nephritis and its underlying mechanism of action. Scopolamine (16 mg/kg) was intraperitoneally injected for induction of Alzheimer’s disease on the 28th day whereas carbamazepine (25 mg/kg) was given daily to induce acute tubulointerstitial nephritis. Treatment with matricin inhibited carbamazepine-induced mRNA expressions of RAS-ERK-MEK-JAK2-STAT3, cytokines (IL-1β, TNF-α, and IL-6), and restored the optimal levels of biomarkers of oxidative stress (MDA, SOD and CAT). Further, matricin treatments reinstated biomarkers of kidney function (creatinine, uric acid, and blood urea nitrogen), and refurbished the levels of MDA, SOD, and CAT. Histopathological analyses indicated that there was systemic dilation, tubular necrosis, interstitial edema, and glomerulus nephritis in the medulla region of the kidneys in rats with Alzheimer’s disease that received carbamazepine only. Treatment with matricin reconsolidated histopathology, and only mild glomerulus nephritis were observed in rats with Alzheimer’s disease. These results suggest that matricin could be utilized as a co-supplement with carbamazepine for the treatment of patients with Alzheimer’s disease to minimize the risk of kidney damage.

Bauhinia L. and Schnella (Raddi.) Wund. are popularly known in Brazil as “mororó”. The leaves and stem bark are used in folk medicine for various purposes, especially against diabetes. Morphoanatomical studies of the leaves of Bauhinia cheilantha (Bong.) Steud., B. pentandra (Bong.) Steud., B. ungulata L. and Schnella outimouta (Aublet) Wund., tribe Cercidae, subtribe Bauhiniinae (Benth.) Walp., were carried out as subsidies to the quality control of their etnodrugs and their derivatives, as well as an additional support to their taxonomy. The morphological and anatomical studies employed traditional techniques of stereo- and light microscopy. All species showed bifoliate leaves, a dorsiventral mesophyll, epidermis with a papillose abaxial surface, anomocytic stomata at the level of the epidermis, and tector trichomes. Schnella outimouta showed leaf characters distinctive from the three species of Bauhinia: indument puberulous on the abaxial surface, leaves hypostomatic, midrib with two collateral bundles, and a cylindrical petiole. The species of Bauhinia have a sericeous-pubescent indument, amphistomatic leaves with boat-shaped glands, midrib with a single bundle, and a canaliculate petiole with lateral projections. Our results provide leaf morphological and anatomical parameters, useful to distinguish the four species studied, which support the quality control of its ethnodrugs.