Alternative Non-Drug Treatment Options of the Most Neglected Parasitic Disease Cutaneous Leishmaniasis: A Narrative Review.

With more than 12 million cases worldwide, leishmaniasis is one of the top 10 neglected tropical diseases. According to the WHO, there are approximately 2 million new cases each year in foci in around 90 countries, of which 1.5 million are cutaneous leishmaniasis (CL). Cutaneous leishmaniasis (CL) is a complex cutaneous condition that is caused by a variety of Leishmania species, including L. (Leishmania) major, L. (L) tropica, L. (L) aethiopica, L. (L) mexicana, L. (Viannia) braziliensis, and L. (L) amazonensis. The disease imposes a significant burden on those who are affected since it typically results in disfiguring scars and extreme social stigma. There are no vaccines or preventive treatments available, and chemotherapeutic medications, including antimonials, amphotericin B, miltefosine, paromomycin, pentamidine, and antifungal medications, have a high price tag, a significant risk of developing drug resistance, and a variety of systemic toxicities. To work around these limitations, researchers are continuously looking for brand-new medications and other forms of therapy. To avoid toxicity with systemic medication use, high cure rates have been observed using local therapy techniques such as cryotherapy, photodynamic therapy, and thermotherapy, in addition to some forms of traditional therapies, including leech and cauterization therapies. These CL therapeutic strategies are emphasized and assessed in this review to help with the process of locating the appropriate species-specific medicines with fewer side effects, lower costs, and elevated cure rates.

Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves: A study supported by DFT calculations and molecular docking.

An ellagitannin monomer, lythracin M (1), and a dimer, lythracin D (2), along with eight known monomers (3-10) were isolated from Lawsonia inermis (Lythraceae) leaves. Lythracin M (1) is a C-glycosidic ellagitannin with a flavogallonyl dilactone moiety that participates in the creation of a γ-lactone ring with the anomeric carbon of the glucose core. Lythracin D (2) was determined as an atropisomer of the reported lythcarin D. These newly discovered structures (1 and 2) were determined by intensive spectroscopic experiments and by comparing DFT-calculated 1H1H coupling, 1H NMR chemical shifts, and ECD data with experimental values. The anti-acetylcholinesterase assay of the compounds 1-10 revealed that the C-1 ellagitannin epimers [casuarinin (7; IC50 = 34 ± 2 nM) and stachyurin (8; IC50 = 56 ± 3 nM)], and the new dimer (2; IC50 = 61 ± 4 nM) possess enzyme inhibitory effects comparable to the reference drug (donepezil, IC50 = 44 ± 3 nM). Molecular docking of compounds 1-10 with AChE identified the free galloyl moiety as an important pharmacophore in the anticholinesterase activity of tannins.

Utilization of Nanotechnology to Improve Bone Health in Osteoporosis Exploiting Nigella sativa and Its Active Constituent Thymoquinone.

Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-α-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasing osteoclast cells. Thymoquinone from N. sativa has exhibited an antioxidant effect on bone tissue by reducing the FeNTA-induced oxidative stress. The present manuscript highlights phytochemistry, pharmacological effect, and the important mechanistic perspective of N. sativa and its active constituents for the management of osteoporosis. Further, it also provides sound discussion on the utilization of a nanotechnology-mediated drug delivery approach as a promising strategy to improve the therapeutic performance of N. sativa and its active constituent, thymoquinone, in the effective management of osteoporosis.

Design, Characterization, and Antimicrobial Evaluation of Copper Nanoparticles Utilizing Tamarixinin a Ellagitannin from Galls of Tamarix aphylla.

The application of plant extracts or plant-derived compounds in the green synthesis of metal nanoparticles (NPs) was researched. Determining the exact metabolite implicated in the formation of NPs would necessitate comprehensive investigations. Copper nanoparticles (CuNPs) are gaining a lot of attention because of their unique properties and effectiveness against a wide range of bacteria and fungi, as well as their potential for usage in catalytic, optical, electrical, and microelectronics applications. In the course of this study, we aimed to formulate CuNPs utilizing pure tamarixinin A (TA) ellagitannin isolated from Tamarix aphylla galls. The main particle size of the formed CuNPs was 44 ± 1.7 nm with zeta potential equal to -23.7 mV, which emphasize the stability of the CuNPs. The X-ray diffraction spectroscopy showed a typical centered cubic crystalline structure phase of copper. Scanning electron microscopy images were found to be relatively spherical and homogeneous in shape. The antimicrobial properties of TA, as well as its mediated CuNPs, have been evaluated through well diffusion assays against four bacterial, Bacillus subtilis NCTC 10400, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, and two fungal, Candida albicans and Aspergillus flavus, strains. The distinctive antimicrobial activities were noted against the fungal strains and the Gram-negative bacterial strains P. aeruginosa ATCC 27853, and E. coli ATCC 25922. In conclusion, CuNPs mediated by TA can be applied for combating a wide range of bacterial and fungal species especially C. albicans, Asp. flavus, and P. aeruginosa in a variety of fields.

Ellagitannins and simple phenolics from the halophytic plant Tamarix nilotica.

Three new [nilotinins M8‒M10 (1‒3)] and two known [tamarixinin A (4) and gemin D (5)] ellagitannins and seven simple phenolics [gallic acid (6), methyl gallate (7), 3,4-di-O-methylgallic acid (8), ellagic acid (9), 3-O-methylellagic acid (10), methyl ferulate 3-O-sulphate (11), and 7,4'-di-O-methylkaempferol (12)] were isolated from the halophytic plant Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae). Their structures were determined based on intensive spectroscopic studies and comparisons with reported data. Compounds 4, and 6-8 were evaluated for their cytotoxicity against lung adenocarcinoma cell line (A549) and anti-leishmanial activity against Leishmania major. Compounds 4, 6 and 7 showed promising cytotoxic properties against A549 (IC50 29 ± 2.3, 10.5 ± 0.7, and 20.7 ± 1.9 µg/mL), while compounds 4 and 7 showed higher growth-inhibitory effects against L. major promastigotes (IC50 40.5 ± 2.7 and 38.4 ± 2.5 µg/mL), as compared with the standards doxorubicin (IC50 0.42 µg/mL) and miltefosine (IC50 9.43 µg/mL), respectively.

Antileishmanial and lung adenocarcinoma cell toxicity of Withania somnifera (Linn.) dunal root and fruit extracts.

This study aims to evaluate the anti-Leishmania major and the lung adenocarcinoma (A549) cytotoxicity of Withania somnifera root and fruit. The total extracts were obtained by homogenisation in aqueous MeOH, and the sub-extracts [n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and methanol (MeOH)] were obtained by flash chromatography. The activity evaluation showed that n-BuOH sub-extracts from root and fruit exhibited noticeable antileishmanial promastigote properties. The n-hexane and EtOAc sub-extracts from both organs, and the MeOH sub-extract from the fruit exerted mild to moderate effects on the promastigotes. In-vitro growth-inhibitory test results on axenic amastigote and cytotoxicity testing on macrophages (RAW264.7), the parasite-host at the amastigote stage, revealed that the activity was mainly concentrated in the root EtOAc and n-BuOH sub-extracts and to a lesser extent the fruit MeOH and EtOAc, and the root n-hexane sub-extracts. Only the roots' EtOAc and n-BuOH sub-extracts demonstrated low cytotoxicity on the A549 cell line.

Two new C-glycosidic ellagitannins and accompanying tannins from Lawsonia inermis leaves and their cytotoxic effects.

Investigation on tannins having antitumor properties led to the isolation of two new C-glycosidic ellagitannins (1 and 2) along with seven known ellagitannins (3-9) and a related polyphenolic constituent (10) from Lawsonia inermis leaves. Our intensive HRESIMS, 1D and 2D NMR, and ECD spectroscopic studies of new tannins have shown that one (1) has a monomer structure of C-glycosidic tannin, and the other (2) has a dimeric structure of 2,3-O-hexahydroxydiphenoyl glucopyranose and a C-glycosidic tannin. Among the known compounds, one (3) is a C-glycosidic tannin that was isolated first of all from nature, five were C-glycosidic tannins, vescalagin (4), 1-O-methylvescalagin (5), castalagin (6), stachyurin (7), and casuarinin (8), and one was an O-glycosidic ellagitannin, tellimagrandin II (9). The remaining phenolic constituent from the leaves was identified as valoneic acid dilactone (10). The ellagitannins 1, and 3-9 demonstrated noticeable cytotoxicity on human oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22), and lower effects on human oral normal cells (HGF, HPC, and HPLF). Tellimagrandin II (9) had the highest tumor-specific cytotoxicity, and also cleaved poly (ADP-ribose) polymerase 1 in HSC-2 cells. These findings showed that L. inermis ellagitannins may be a candidate for the production of anti-oral cancer materials.

Cytotoxic polyhydroxy sterols from the Egyptian Red Sea soft coral Sarcophyton acutum.

The methanolic extract and its sub-extracts (viz, n-hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti-Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1-6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3-6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC50 17.2 ± 1.5 µg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8-57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols.

Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions.

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TAXONOMY: Functional Disorder, Traditional Medicine, Herbal Medicine.

Knowledge about COVID-19 and beliefs about and use of herbal products during the COVID-19 pandemic: A cross-sectional study in Saudi Arabia.

The lack of treatment options for COVID-19 has raised many concerns among populations worldwide, which has led to many attempts to find alternative options to prevent the transmission of the disease or to alleviate the progression of the infection, including focusing more on preventive measures (to prevent transmission to other individuals) and the use of natural products and herbal extracts to increase immunity and decrease the probability of getting infected. This study explored the knowledge of the population of the Kingdom of Saudi Arabia (KSA) about COVID-19 preventive measures and their belief about the consumption of herbal products for the prevention of COVID-19 infection. A total of 5,258 individuals participated in this study. Participants' knowledge about the appropriate COVID-19 preventive measures in terms of handwashing procedures, self-quarantine and social distancing was moderate, with a mean score of 5.5 (SD: 1.7) out of 10 (representing around 55.0% of the total score). About 22.1% (n = 1,161) of the participants reported that they have used herbal products or nutritional supplements during the pandemic period, to protect themselves from the disease. Social media and the Internet (39.4%, n = 372) were the main motivators for the participants to try herbal products. Vitamin C was the most commonly used food supplement to increase immunity and reduces the chance of contracting COVID-19. Our study demonstrated that the general population in Saudi Arabia has a moderate level of knowledge about COVID-19 transmission and preventive measures. A considerable proportion of the population reported the use of herbal products or food supplements in order to protect themselves from the disease. Policymakers are suggested to provide further educational campaigns that increase population knowledge about the disease transmission routes and preventive measures. In addition, the use of herbal products should be evidence-based to ensure patient safety.

Anti-Alzheimer's flavanolignans from Ceiba pentandra aerial parts.

Four flavanolignans, ceibapentains A (1) and B (2) and cinchonains Ia (3) and Ib (4), were isolated for the first time from an ethyl acetate extract of Ceiba pentandra (L) (Bombacaceae) aerial parts. The ceibapentains A (1) and B (2) are new compounds and their structures, including the absolute configurations, were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism analyses, then compared with reported data. Compounds 1-4 were tested for their anti-Alzheimer's activity via an assessment of their inhibitory effect on amyloid ß42 aggregation using a thioflavin T assay. The results revealed that cinchonain Ia (3) showed a higher inhibitory effect (91%) than the standard curcumin (70%). Compounds 1, 2, and 4 exhibited moderate activity, with inhibition ratios of 43%, 47%, and 58%, respectively. A molecular docking study on the binding mode of 3 and curcumin with an amyloid ß1-40 peptide fibril structure indicated a high affinity of cinchonain 1a (3) towards amyloid ß1-40 peptide, in agreement with the experimental results.

Ellagitannins, gallotannins, and gallo-ellagitannins from the galls of Tamarix aphylla.

Chromatographic separation of an aqueous acetone extract of the galls from Tamarix aphylla using gels resulted in isolation of an ellagitannin, phyllagallin M1 (13), a gallo-ellagitannin, phyllagallin D1 (14), and four gallotannins, phyllagallin M2 (15) and phyllagallins D2-D4 (16-18), in addition to four known ellagitannins and three phenolics of lower molecular weight structurally related to hydrolyzable tannins. The structures of the six new tannins were elucidated based on spectroscopic and chemical data. Among the phenolics, flavogallonic acid dilactone (8), which is presumed to be biogenetically produced by C-C oxidative coupling of an ellagic acid unit with a galloyl residue, shows an exceptional oxidative pattern of gallic acid residues in plants of the family Tamaricaceae. Although the ellagitannin tamarixellagic acid (4) was reported to be a constituent of the galls of T. aphylla, such compounds with anomalous location of the DHDG moiety at O-3 on the glucopyranose core have not been observed among the tannins of tamaricaceous plants.

Structures of new phenolics isolated from licorice, and the effectiveness of licorice phenolics on vancomycin-resistant Enterococci.

Licorice, which is the underground part of Glycyrrhiza species, has been used widely in Asian and Western countries as a traditional medicine and as a food additive. Our continuous investigation on the constituents of roots and stolons of Glycyrrhiza uralensis led to the isolation of two new phenolics, in addition to 14 known compounds. Structural studies including spectroscopic and simple chemical derivatizations revealed that both of the new compounds had 2-aryl-3-methylbenzofuran structures. An examination of the effectiveness of licorice phenolics obtained in this study on vancomycin-resistant strains Enterococcus faecium FN-1 and Enterococcus faecalis NCTC12201 revealed that licoricidin showed the most potent antibacterial effects against both of E. faecalis and E. faecium with a minimum inhibitory concentration (MIC) of 1.9 × 10-5 M. 8-(γ,γ-Dimethylallyl)-wighteone, isoangustone A, 3'-(γ,γ-dimethylallyl)-kievitone, glyasperin C, and one of the new 3-methyl-2-phenylbenzofuran named neoglycybenzofuran also showed potent anti-vancomycin-resistant Enterococci effects (MIC 1.9 × 10-5-4.5 × 10-5 M for E. faecium and E. faecalis). The HPLC condition for simultaneous detection of the phenolics in the extract was investigated to assess the quality control of the natural antibacterial resource, and quantitative estimation of several major phenolics in the extract with the established HPLC condition was also performed. The results showed individual contents of 0.08%-0.57% w/w of EtOAc extract for the major phenolics in the materials examined.

Structures of two new flavonoids and effects of licorice phenolics on vancomycin-resistant Enterococcus species.

Since our previous study revealed that several licorice phenolics have antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA), and suppressive effects on the oxacillin resistance of MRSA, we further investigated effectiveness of licorice constituents on vancomycin-resistant Enterococcus (VRE) bacteria, and purified 32 phenolic compounds. Two flavonoids among them were characterized structurally, and identified their structures as demethylglycyrol (31) and 5,7-di-O-methylluteone (32), respectively. Examination of antibacterial effects of licorice phenolics showed that 3-arylcoumarins such as licoarylcoumarin (9) and glycycoumarin (26), and 2-arylcoumarones such as gancaonin I (17), have moderate to potent antibacterial effects on the VRE strains used in this study.

Hydrolyzable tannins of tamaricaceous plants. III. Hellinoyl- and macrocyclic-type ellagitannins from Tamarix nilotica.

Three new hellinoyl-type ellagitannins, nilotinins M4 (7), D7 (8), and D8 (9), and a new macrocyclic-type, nilotinin D9 (10), together with eight known tannins, hirtellins B (2), C (11), and F (12), isohirtellin C (13), tamarixinin A (3), tellimagrandins I and II, and 1,2,6-tri-O-galloyl-beta-d-glucose (14), were isolated from an aqueous acetone extract of Tamarix nilotica dried leaves. Nilotinin M4 (7) is a monomeric tannin possessing a hellinoyl moiety. The structure of 8 demonstrated replacement of one of the HHDP groups at the glucose core O-4/O-6 in ordinary dimeric tannins with a galloyl moiety at O-6. This is a new structural feature among the tamaricaceous ellagitannins. On the basis of the results, reported spectroscopic assignments for 2, 3, and the macrocyclic tannins 11-13 were revised. Unusual shifts in the NMR spectra of these macrocyclic tannins are also discussed in relation to their conformations. Several tannins isolated from T. nilotica were assessed for possible cytotoxic activity against four human tumor cell lines, and nilotinin D8 (9) and hirtellin A (1) showed high cytotoxic effects.