Search

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats' model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-β, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug., (© 2024 The Author(s).)

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Orabi, Abouelela, Darwish, Abdelkader, Elsadek, Al Awadh, Alshahrani, Alhasaniah, Aldabaan and Abdelhamid.)

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC 50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC 50 = 69.4 μM and melphalan at CC 50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG 1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D ( 18 ) and O ( 12 ), and the flavonoid kaempferol ( 11 ). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera 's potential as an affordable source of therapeutic agents for a range of oral malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AE-B declared a shared affiliation with the author(s) MA and RA to the handling editor at the time of review., (Copyright © 2024 Al Awadh, Sakagami, Amano, Sayed, Abouelela, Alhasaniah, Aldabaan, Refaey, Abdelhamid, Khalil, Hamdan, Abdel-Sattar and Orabi.)

Lignan phytomolecules demonstrate promising anti-Alzheimer activity by alleviating dementia and preserving nerve cells. The purpose of this work is to characterize the lignans of Anisacanthus virgularis and explore their potential anti-acetylcholinesterase and anti-ageing effects. Phytochemical investigation of A. virgularis aerial parts afforded a new furofuranoid-type lignan ( 1 ), four known structural analogues, namely pinoresinol ( 2 ), epipinoresinol ( 3 ), phillyrin ( 4 ), and pinoresinol 4- O - β -d-glucoside ( 5 ), in addition to p -methoxy- trans -methyl cinnamate ( 6 ) and 1H-indole-3-carboxaldehyde ( 7 ). The structures were established from thorough spectroscopic analyses and comparisons with the literature. Assessment of the anticholinesterase activity of the lignans 1 - 5 displayed noticeable enzyme inhibition of 1 (IC 50 = 85.03 ± 4.26 nM) and 5 (64.47 ± 2.75 nM) but lower activity of compounds 2 - 4 as compared to the reference drug donepezil. These findings were further emphasized by molecular docking of 1 and 5 with acetylcholinesterase (AChE). Rapid overlay chemical similarity (ROCS) and structure-activity relationships (SAR) analysis highlighted and rationalized the anti-AD capability of these compounds. Telomerase activation testing of the same isolates revealed 1.64-, 1.66-, and 1.72-fold activations in cells treated with compounds 1 , 5 , and 4 , respectively, compared to untreated cells. Our findings may pave the way for further investigations into the development of anti-Alzheimer and/or anti-ageing drugs from furofuranoid-type lignans.

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves' 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H 2 O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound ( 1 ) along with tannin-related metabolites, benzoic acid ( 2 ), benzyl 6'- O -galloyl- β -D-glucopyranoside ( 3 ), and ellagic acid ( 4 ), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O -glucosidic ellagitannins, heterophylliin A ( 5 ), and gemin D ( 6 ), in addition to four known C -glycosidic ellagitannins, lythracin D ( 7 ), pedunculagin ( 8 ), flosin B ( 9 ), and lagerstroemin ( 10 ). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D ( 1 H and 13 C) and 2D ( 1 H- 1 H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α] D , and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a β -ionone, a degradative product of the common metabolite β -carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 ( 7 ) and pedunculagin ( 8 ) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders.

Dietary fruits and vegetables play a vital role as food and drugs and are the main sources of antioxidant defences against degenerative diseases, such as brain dysfunctions, cardiovascular diseases, immune system deteriorations, and cancers, brought on by oxidative damage. Phyllanthus emblica is a significant herbal remedy used in conventional medicine to recover lost strength and power. In this research, the potential value of Phyllanthus emblica as a food and drug is researched. The total phenolic, total flavonoid, and total tannin contents as well as the nutritional value, vitamin C, vitamin E, and mineral contents of different organs of P. emblica were evaluated. The antioxidant and antimicrobial activities of extracts and fractions of different organs of P. emblica were determined. A total of eleven flavonoids, simple phenolic, tannin-related phenolic, and tannin molecules were isolated from a hydroalcoholic extract of the leaves and fruits. The structures were identified by spectroscopic data and comparison with the literature values as gallic acid ( 1 ), naringenin 7- O -(6″- O -galloyl)- β -D-glucopyranoside ( 2 ), 3,3'-di- O -methyl ellagic acid-4'- O - β -d-glucopyranoside ( 3 ), 1- O -galloyl glycerol ( 4 ), 1,6-di- O -galloyl- β -d-glucopyranoside ( 5 ), flavogallonic acid bislactone ( 6 ), corilagin ( 7 ), ethyl gallate ( 8 ), urolithin M5 ( 9 ), (E)- p -coumaroyl-1- O - β -d-glucopyranoside ( 10 ), and 1,2,4,6-tetra- O -galloyl- β -d-glucopyranoside ( 11 ). Among them, compounds 3 and 10 are first isolated from the plant. Molecular docking was performed to investigate the comparative interactions between positive controls (galantamine and donepezil) and selected compounds utilizing acetylcholinesterase (4EY7) as a target receptor. Results exhibited the potency of these compounds against the target receptor. In summary, P. emblica has a wealth of minerals, vitamins C and E, and polyphenolic phytochemicals that may work together to treat infectious disease, prevent and/or treat oxidative-damage-related illnesses including Alzheimer's disease.

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.

The plain 5-fluorouracil (5FU) formulations available in the market are associated with adverse effects such as skin irritation, pruritus, redness, blisters, allergy, and dryness on the site of application. The objective of the present study was to develop a liposomal emulgel of 5FU with increased skin permeability and efficacy using clove oil and eucalyptus oil along with pharmaceutically acceptable carriers, excipients, stabilizers, binders, and additives. A series of seven formulations were developed and evaluated for their entrapment efficiency, in vitro release profile, and cumulative drug release profile. The compatibility of drugs and excipients, as confirmed by FTIR (fourier-transform infrared spectroscopy) and DSC (differential scanning calorimetry) as well as SEM (scanning electron microscopy) and TEM (transmission electron microscopy) studies, revealed that the size and shape of liposomes are smooth and spherical, and the liposomes are non-aggregated. To understand their efficacy, the optimized formulations were evaluated for cytotoxicity using B16-F10 mouse skin melanoma cells. The eucalyptus oil and clove oil-containing preparation significantly produced a cytotoxic effect against a melanoma cell line. The addition of clove oil and eucalyptus oil increased the efficacy of the formulation by improving skin permeability and reducing the dose required for the anti-skin cancer activity.

Leishmaniasis is a group of infectious diseases caused by Leishmania protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. Leishmania N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. Withania somnifera leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against Malaria, Trypanosoma , and Leishmania spp. Through a review of previously reported compounds from W. somnifera -afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the Withania genus. These compounds were subjected to molecular docking screening and molecular dynamics against L. major NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to L. major NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.

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 1 H 1 H coupling, 1 H 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; IC 50  = 34 ± 2 nM) and stachyurin (8; IC 50  = 56 ± 3 nM)], and the new dimer (2; IC 50  = 61 ± 4 nM) possess enzyme inhibitory effects comparable to the reference drug (donepezil, IC 50  = 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohamed A. A. Orabi reports financial support was provided by Najran University. Mohamed A. A. Orabi reports a relationship with Najran University that includes: employment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Lung cancer and cutaneous leishmaniasis are critical diseases with a relatively higher incidence in developing countries. In this research, the activity of Carissa macrocarpa leaf hydromethanolic extract and its solvent-fractions ( n -hexane, EtOAc, n -butanol, and MeOH) against the lung adenocarcinoma cell line (A549) and Leishmania major was investigated. The MeOH fraction exhibited higher cytotoxic activity (IC 50 1.57 ± 0.04 μg/mL) than the standard drug, etoposide (IC 50 50.8 ± 3.16 μg/mL). The anti- L. major results revealed strong growth inhibitory effects of the EtOAc fraction against L. major promastigotes (IC 50 27.52 ± 0.7 μg/mL) and axenic amastigotes (29.33 ± 4.86% growth inhibition at 100 μg/mL), while the butanol fraction exerted moderate activity against promastigotes (IC 50 73.17 ± 1.62), as compared with miltefosine against promastigotes (IC 50 6.39 ± 0.29 μg/mL) and sodium stibogluconate against axenic amastigotes (IC 50 22.45 ± 2.22 μg/mL). A total of 102 compounds were tentatively identified using UPLC-ESI-MS/MS analysis of the total extract and its fractions. The MeOH fraction was found to contain several flavonoids and flavan-3-ol derivatives with known cytotoxic properties, whereas the EtOAc fractions contained triterpene, hydroxycinnamoyl, sterol, and flavanol derivatives with known antileishmanial activity. Molecular docking of various polyphenolics of the MeOH fraction with HDAC6 and PDK3 enzymes demonstrates high binding affinity of the epicatechin 3- O -β-D-glucopyranoside and catechin-7- O -β-D-glucopyranoside toward HDAC6, and procyanidin C2, procyanidin B5 toward PDK3. These results are promising and encourage the pursuit of preclinical research using C. macrocarpa 's MeOH fraction as anti-lung cancer and the EtOAc fraction as an anti- L. major drug candidates.

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.

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.

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene ( 1 ), two known analogues [sarcotrocheliol ( 2 ) and sarcophine ( 3 )], and two sterols [(24 S )-24-methylcholesterol ( 4 ) and gorgosterol ( 5 )]. The structure of the new diterpene ( 1 ) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC 50 17.4 ± 1.9 µg/ml) and HepG2 (IC 50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC 50 >100 µg/ml).

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.

A total methanolic extract and its sub-extracts of Orobanche crenata (Forssk.) aerial parts were subjected to acute toxicity, anti-inflammatory, and hepatoprotective investigations. The methanolic extract was safe upto 3 g/kg on mice. The EtOAc fraction reduced the carrageenan-induced rat paw edema better than indomethacin. It also demonstrated a drop in the elevated ALT, AST, and TB at 300 mg/kg, better than silymarin. Histopathological examination of liver cells of rats given the EtOAc fraction showed a complete absence of the CCl 4 -induced cloudy swelling. A phytochemical investigation of the n -hexane and EtOAc fractions yielded 11 compounds [indole-3-carboxylic acid ( 1 ), n -butyl palmitate ( 2 ), tyrosol ( 3 ), L-rhamnonic acid-1,4-lactone ( 4 ), β -sitosterol/stigmasterol mixture ( 5/5' ), β -sitosterol/stigmasterol glycosides mixture ( 6/6 '), chrysoeriol ( 7 ), luteolin ( 8 ), apigenin ( 9 ), crenatoside ( 10 ), and verbascoside ( 11 )] as identified by UV, 1D & 2D NMR and ESIMS techniques. Their reported biological actions were in relation to and supported our herein detected pharmacological findings.

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 (IC 50 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 (IC 50 40.5 ± 2.7 and 38.4 ± 2.5 μg/mL), as compared with the standards doxorubicin (IC 50 0.42 µg/mL) and miltefosine (IC 50 9.43 μg/mL), respectively.

Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the C. macrocarpa leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the C. macrocarpa leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acetylcholinesterase (AChE) inhibitor and telomerase reverse transcriptase (TERT) potentiator phytochemicals are highly targeted as anti-Alzheimerꞌs disease and as an anti-ageing process. A phytochemical study of Thunbergia erecta aerial parts resulted in the isolation of ten compounds (1-10). Their structures were identified based on spectral data and comparison with literature values. The activity of our pure isolates on AChE and TERT enzymes by documented in vitro assay methods were evaluated. The results indicated that apigenin (2), vanillic acid (4), and acacetin-7-O-β-D-glucoside (7) exhibited potent inhibition of AChE (IC 50 37.33, 30.80 and 49.57 ng/mL, respectively), compared to the standard drug donepezil (IC 50 31.25 ng/mL). In the TERT enzyme assay, compound 7 triggered a 1.66‑fold increase in telomerase activity at the concentration of 2.85 ng/ml. This is the first study that demonstrates that compound 7 isolated from T. erecta can lead to such telomerase activity relative to control cells. Virtual screening studies including docking, rapid overlay chemical structure (ROCS), and calculated structure-property relationships (SPR) were implemented in this work. Molecular docking studies supported the binding of compounds 2, 4, and 7 through hydrogen bonds (HBs) formation to essential amino acid residues namely ARG:24 A, SER:347 A, LYS:51 A, PHE:346 A, and GLY:345 A of acetylcholinesterase. ROCS and SPR analyses realized compound 2 as a possible treatment of Alzheimer's disease and as a lead compound for drug development process through applying semisynthetic modifications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

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 (IC 50 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Considering the transmissible nature of COVID-19 it is important to explore the trend of the epidemiology of the disease in each country and act accordingly. This study aimed to examine the trend of COVID-19 epidemiology in the Kingdom of Saudi Arabia in term of its incidence rate, recovery rate, and mortality rate. Material and Methods: We conducted an observational study using publicly available national data taken from the Saudi Ministry of Health for the period between 3 March and 7 June 2020. The number of newly confirmed cases, active cases, critical cases, percentage of cases stratified by age group [adults, children, and elderly] and gender were extracted from the reports of the Saudi Ministry of Health. Results: During the study period, the total number of confirmed cases with COVID-19 rose from one on 2 March 2020 to 101,914 on 7 June, representing an average of 1,039 new cases per day, [trend test, p < 0.000]. Despite the increase in the number of newly confirmed daily cases of COVID-19, the number of reported daily active cases started to stabilize after 2 months from the start of the pandemic in the country and the overall recovery rate was 71.4%. The mortality rate decreased by 6.4% during the study period. COVID-19 was more common among adults and males compared to other demographic groups. Conclusion: The epidemiological status of COVID-19 in the Kingdom of Saudi Arabia showing promising improvement. Males and adults accounted for the majority of COVID-19 cases in the KSA. Further studies are recommended to be conducted at the patient level to identify other patient groups who are at higher risk of getting infected with COVID-19, and for whom the best pharmacological intervention could be provided., (Copyright © 2020 Alyami, Naser, Orabi, Alwafi and Alyami.)

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 β42 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 β1-40 peptide fibril structure indicated a high affinity of cinchonain 1a (3) towards amyloid β1-40 peptide, in agreement with the experimental results., Competing Interests: Declaration of Competing Interest The authors publicize no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ellagitannin oligomers are large molecules habitually showing complex NMR spectra that are sometimes misinterpreted and lead to incorrect structures. Understanding the NMR spectroscopic features of a group of ellagitannins would overcome these inadequacies. In this study, investigation of the galls of Tamarix aphylla led to the isolation of three new ellagitannin oligomers, phyllagallins T1 ( 1 ), T2 ( 2 ), and Q1 ( 3 ), a known monomer nilotinin M4 ( 4 ), four known dimers, nilotinins D7 ( 5 ) and D8 ( 6 ), hirtellin B ( 7 ), and tamarixinin A ( 8 ), and a simple phenolic, dehydrotrigallic acid ( 9 ). 1D and 2D NMR, HRESI-TOFMS, and ECD experiments show that compounds 1 - 8 are hellinoyl-type ellagitannins. The NMR spectroscopic features of this type of ellagitannins and the reasons for the abnormal upfield shifts of glucose anomeric proton and hellinoyl moiety proton signals are established considering the experimental results as well as quantum chemical calculation on a simple hellinoyl-type monomer, phyllagallin M2. Based on these results, the NMR assignments reported previously by a different research group for bracteatinin T 1 and hirtellin T 3 are revised. A cytotoxicity study against human oral squamous cell carcinoma cell lines (Ca9-22, HSC-2, and HSC-4) and human mesenchymal normal oral cells (HGF, HPC, and HPLF) showed cytotoxic effects with tumor-specificity higher than 5.2, 3.0, 1.6, and 2.0 for compounds 5 , 2 , 9 , and 3 , respectively.

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 (IC 50  = 0.0716) comparable to those of the standard natural (ascorbic acid, IC 50  = 0.045) and synthetic (BHA, IC 50  = 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., (© 2019 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)