Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract.

The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract's impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass.

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

Investigation of phytochemicals isolated from selected Saudi medicinal plants as natural inhibitors of SARS CoV-2 main protease: In vitro, molecular docking and simulation analysis.

The escalation of many coronavirus variants accompanied by the lack of an effective cure has motivated the hunt for effective antiviral medicines. In this regard, 18 Saudi Arabian medicinal plants were evaluated for SARS CoV-2 main protease (Mpro) inhibition activity. Among them, Terminalia brownii and Acacia asak alcoholic extracts exhibited significant Mpro inhibition, with inhibition rates of 95.3 % and 95.2 %, respectively, at a concentration of 100 µg/mL. Bioassay-guided phytochemical study for the most active n-butanol fraction of T. brownii led to identification of eleven compounds, including two phenolic acids (1, and 2), seven hydrolysable tannins (3-10), and one flavonoid (11) as well as four flavonoids from A. asak (12-15). The structures of the isolated compounds were established using various spectroscopic techniques and comparison with known compounds. To investigate the chemical interactions between the identified compounds and the target Mpro protein, molecular docking was performed using AutoDock 4.2. The findings identified compounds 4, 5, 10, and 14 as the most potential inhibitors of Mpro with binding energies of -9.3, -8.5, -8.1, and -7.8 kcal mol-1, respectively. In order to assess the stability of the protein-ligand complexes, molecular dynamics simulations were conducted for a duration of 100 ns, and various parameters such as RMSD, RMSF, Rg, and SASA were evaluated. All selected compounds 4, 5, 10, and 14 showed considerable Mpro inhibiting activity in vitro, with compound 4 being the most powerful with an IC50 value of 1.2 µg/mL. MM-GBSA free energy calculations also revealed compound 4 as the most powerful Mpro inhibitor. None of the compounds (4, 5, 10, and 14) display any significant cytotoxic activity against A549 and HUVEC cell lines.

Isolation of a novel isoprenylated phenolic compound and neuroprotective evaluation of Dodonaea viscosa extract against cerebral ischaemia-reperfusion injury in rats.

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-ß-D-apiosyl-(1''' â†’ 6'')- ß-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways.

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

Cardioprotective study of Eriobotrya japonica leaf extracts against carbon tetrachloride induced toxicity in rats.

The Rosaceae family includes the evergreen subtropical tree known as Eriobotrya japonica Lindl (loquat). To test the effect of several E. japonica leaf extracts on shielding the heart from carbon tetrachloride (CCl4) cytotoxic effects, we employed carbon tetrachloride (CCl4), a highly toxic chemical, to cause cardiotoxicity in rats. The heart function enzymes that were examined were lactate dehydrogenase (LDH) and Creatine Kinase. When compared to both the hazardous and normal groups, it was discovered that the protective dose of ethyl acetate extract (200 mg/Kg) and aqueous extract (100 and 200 mg/Kg) lowered the cardiac indicators. Total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) indicators were used to assess myocardial oxidative stress. Rats pretreated with ethyl acetate (200 mg/Kg) and aqueous extract (100 and 200 mg/Kg) showed higher levels of total protein than the control group. When compared to the silymarin group, all of the loquat leaf extracts examined in this study increased the amount of the MDA enzyme. The data also demonstrated that, when compared to the results from the normal group, aqueous extract (100 and 200 mg/Kg) enhanced the amount of NP-SH. The histopathology showed that administration of all loquat leaf extracts at doses of (100 mg/kg, 200 mg/kg) before CCl4 intoxication greatly reduced the modifications that were exhibited by CCl4 and preserved cardiac muscles that were very equivalent to those of normal control. Based on the aforementioned data, we deduced that loquat leaf aqueous extract provided the highest protection for heart tissue against the effects of CCl4 intoxication. Through chemical examination of the methanolic extract, four flavonoids were extracted and identified. Their structures were found to be kaempferol-3-O-rhamnoside 1, quercetin-3-O-rhamnoside 2, quercetin-3,7 di-O-glycerides 3, and roseoside 4.

Mechanisms of anti-ulcer actions of Prangos pabularia (L.) in ethanol-induced gastric ulcer in rats.

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

Multi-target mechanism of Solanum xanthocarpum for treatment of psoriasis based on network pharmacology and molecular docking.

Solanum xanthocarpum (SX) has been used to treat a variety of diseases, including skin disorders like psoriasis (PSO). SX possesses many pharmacological activities of anti-inflammatory, anti-cancer, immunosuppressive, and healing qualities. However, the multi-target mechanism of SX on PSO still needs clarity. Materials and methods: The Indian Medicinal Plants, Phytochemicals and Therapeutics (IMPPAT) database and the Swiss Target Prediction online tool were used to find the active phytochemical components and their associated target proteins. OMIM and GeneCards databases were used to extract PSO-related targets. A Venn diagram analysis determined the common targets of SX against PSO. Subsequently, the protein-protein interaction (PPI) network and core PPI target analysis were carried out using the STRING network and Cytoscape software. Also, utilising the online Metascape and bioinformatics platform tool, a pathway enrichment analysis of common targets using the Kyoto Encyclopaedia of Genes and Genome (KEGG) and Gene Ontology (GO) databases was conducted to verify the role of targets in biological processes, cellular components and molecular functions with respect to KEGG pathways. Lastly, molecular docking simulations were performed to validate the strong affinity between components of SX and key target receptors. Results: According to the IMPPAT Database information, 8 active SX against PSO components were active. According to the PPI network and core targets study, the main targets against PSO were EGFR, SRC, STAT3, ERBB2, PTK2, SYK, EP300, CBL, TP53, and AR. Moreover, molecular docking simulations verified the binding interaction of phytochemical SX components with their PSO targets. Last but not least, enrichment analysis showed that SX is involved in several biological processes, including peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, and peptidyl-serine modification. The relevant KEGG signalling pathways are the PI3K-AKT signalling pathway, the EGFR tyrosine kinase inhibitor resistance pathway, and the MAPK signalling pathway. Conclusion: The network pharmacology technique, which is based on data interpretation and molecular docking simulation techniques, has proven the multi-target function of SX phytoconstituents.

Revisiting the Flora of Saudi Arabia: Phytochemical and Biological Investigation of the Endangered Plant Species Euphorbia saudiarabica.

Euphorbia plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current study, a phytochemical investigation of Euphorbia saudiarabica methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl3) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (2), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the E. saudiarabica crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the E. saudiarabica CHCl3 and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC50 values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells' proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (1) showed potent activity against the MCF-7 cell line, with an IC50 value of 9.83 µg/mL. Our findings suggest that E. saudiarabica has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.

Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats.

Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF.

Bioguided isolation of potential antitumor agents from the aerial parts of cultivated cardoon (Cynara cardunculus var. altilis).

Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide; therefore, searching for an effective treatment for this illness is of great importance. In the present work, in vitro cytotoxic activity of the ethanol extract of the aerial parts of Cynara cardunculus L. against human liver carcinoma cells (Hep G2) was tested. Additionally, the antitumor activity of the extract was confirmed using chemically induced rat liver carcinogenesis with diethylnitrosamine (DEN). Moreover, bioguided fractionation and column chromatographic separation of the active compounds were carried out. The extract of C. cardunculus showed a promising cytotoxic activity according to the protocols of the National Cancer Institute. Bioguided chromatographic separation of the ethanol extract of C. cardunculus led to the isolation of seven secondary metabolites including two sesquiterpene lactones as the principal active components of the methylene chloride soluble fraction, grosheimin (IC50 = 7.49 µg/mL) and cynaropicrin (IC50 = 13.9 µg/mL). The compounds were characterized by different spectroscopic techniques such as EI-MS, IR and NMR. Additionally, in silico analysis of the two active compounds revealed their ability to bind with caspase-3 via hydrogen bonds interactions to initiate apoptosis of cancer cells. The results shed the light on the significance of C. cardunculus as a potential source of antitumor agents.

Synthesis of Silver Nano Particles Using Myricetin and the In-Vitro Assessment of Anti-Colorectal Cancer Activity: In-Silico Integration.

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3', 4', 5,5', and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin's effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.

Unprecedented Insights on Chemical and Biological Significance of Euphorbia cactus Growing in Saudi Arabia.

Euphorbia cactus Ehrenb ex Boiss. is a plant species reported from central Africa and the southern Arabian Peninsula, belonging to the family of Euphorbiaceae. The plant has ethnobotanical values and is well-known for its milky latex, which has been turned into medicine to treat various ailments. To the best of our knowledge, there have been no literature reports available on phytochemical constituents and antiproliferative mechanism of E. cactus. In the current study, the phytochemical investigation of E. cactus methanolic extract (ECME) resulted in the isolation and characterization of four secondary metabolites, which are reported for the first time from this plant species. In addition, the results of 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and ferrous ion chelating (FIC) assays expressed maximum antioxidant activity by ECME and the isolated phytochemicals. Furthermore, ECME exerted a promising antiproliferative effect against different cancer cell lines, and the A549 lung cancer cells were the most sensitive with an IC50 value of 20 µg/mL. The antiproliferative action of ECME in A549 cells was associated with cell accumulation in the G2/M phase and an increase in early and late apoptosis. In addition, RT-PCR and western blot analysis revealed that ECME decreased the anti-apoptotic (Bcl-2) expression, while the expression of pro-apoptotic (Bax) and caspase-3 were increased. This study provides the first insight into the phytochemical constituents and the antiproliferative mechanism of ECME, implying that it could be exploited as a promising natural source for developing new cancer therapies. Further preclinical research is warranted to support the current results.

Probing PXR activation and modulation of CYP3A4 by Tinospora crispa and Tinospora sinensis.

ETHNOPHARMACOLOGICAL RELEVANCE: The two Tinospora species, T. crispa and T. sinensis, native to Southeast Asia, are integral components of various traditional preparations with structure-function claims to treat various disorders, including diabetes and inflammation. AIM OF THE STUDY: To assure the safety of the botanicals finished products, herb-drug interaction potential of T. crispa and T. sinensis was investigated by testing their extracts and compounds for in vitro activation of the pregnane X-receptor (PXR) and the modulation of CYP3A4 isozyme, selectively. MATERIALS AND METHODS: A total of sixteen fully characterized phytochemicals from T. crispa and T. sinensis were evaluated for PXR activation by luciferase reporter gene assay. CYP3A4 inhibition studies were carried out for eleven compounds. In addition, docking studies were performed to elucidate the possible binding modes to the PXR by the compounds using computational methods. RESULTS: Significant activation of PXR (2-fold) was observed for both extracts and non-polar fractions of T. crispa. Among the pure compounds, columbin showed highest activation of PXR (3-fold), which was comparable with the positive control, rifampicin. Vital interactions were predicted with docking simulation of PXR-columbin complex with critical amino acid residues (Trp-299) that are known for the activation of PXR. The methanolic extracts of T. crispa and T. sinensis also showed considerable CYP3A4 inhibition. CONCLUSION: T. crispa and T. sinensis, both demonstrated the potential to mediate herb-drug interaction through PXR activation and inhibition of CYP3A4 isozyme. Moreover, the elucidation of the potential to induce herb-drug interaction, by the phytochemicals of these Tinospora plants, thereby supports the need for further investigation to establish the clinical relevancy of these constituents for possible adverse interactions with pharmaceutical drugs.

Serum Proteomic Analysis of Cannabis Use Disorder in Male Patients.

Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.

Metabolic profiling and biological activities of the aerial parts of Micromeria imbricata Forssk. growing in Saudi Arabia.

The hydroalcoholic extract (MIT) of Micromeria imbricata (Forssk.) growing in Saudi Arabia in addition to the chloroform (MIC) and n-butanol (MIB) fractions were investigated for the first time using UPLC-ESI-MS/MS. The analysis revealed the tentative identification of fifty-eight compounds including three organic acids, twenty-five phenolic compounds, three coumarins, two anthocyanins, twenty-one flavonoids, three terpenes, and one miscellaneous. Moreover, the therapeutic potential of M. imbricata (MIT) and its fractions (MIC and MIB) were determined by in vitro evaluation of their cytotoxic, antioxidant, and anti-obesity characteristics. The MIT extract showed the highest phenolic (125.23 ± 0.87 mg gallic acid equivalent/100 gm extract) and flavonoid (112.24 ± 2.45 mg quercetin equivalent/100 gm extract) contents followed by n-butanol and chloroform fractions. The MIT extract revealed a potent cytotoxic activity against HepG-2 (Hepatocellular carcinoma) and MCF-7 (Breast carcinoma) with IC50 28.5 ± 2.0 and 35.2 ± 1.2 µg/mL, respectively. Additionally, the tested hydroalcoholic extract exhibited a significant DPPH scavenging activity with SC50 28.4 ± 1.2 µg/mL and a remarkable lipase inhibitory activity with IC50 54.2 ± 1.2 µg/mL. In conclusion, the current study presents the first insights into the phytochemical constituents and pharmacological properties of M. imbricata extract and its chloroform and n-butanol fractions. The results revealed that M. imbricata hydroalcoholic extract might be a prolific source of bioactive constituents with potent antioxidant, cytotoxic and anti-obesity potential. It might be a natural alternative therapy and nutritional strategy for obesity treatment.

Protective effect of diosmin against doxorubicin-induced nephrotoxicity.

Doxorubicin (Dox) is an anthracycline antibiotic that is primarily used for treating various solid tumors including that of pulmonary, ovary, breast, uterine, cervix, and several blood cancers. However, nephrotoxicity associated with Dox treatment limits its clinical use. Administration of Dox in combination with compounds exhibiting antioxidant properties are being used to minimize the side effects of Dox. Diosmin is a flavonoid glycoside with numerous beneficial properties that is found in the pericarp of many citrus fruits. Diosmin has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects in response to various insults, although the exact mechanism remains unknown. Therefore, this study was designed to evaluate the effect of diosmin in preventing kidney damage in response to Dox treatment. Male Wistar rats were randomly divided into four groups: control group, Dox group (20 mg/kg, i.p.), Dox plus low-dose diosmin group (100 mg/kg orally), and Dox plus high-dose diosmin group (200 mg/kg orally). A single intraperitoneal injection of Dox resulted in kidney damage as evidenced by significant alterations in kidney markers, histological abnormalities, and the attenuation of antioxidant defense mechanisms (GSH, SOD, and CAT). Moreover, Dox treatment significantly altered the expression of oxidative stress, inflammatory, and anti-apoptotic protein markers. Diosmin pretreatment alleviated Dox-induced nephrotoxicity by ameliorating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring kidney architecture. In conclusion, our results indicate that diosmin is a promising therapeutic agent for the prevention of nephrotoxicity associated with DOX.

(E)-2,6,10-Trimethyldodec-8-en-2-ol: An Undescribed Sesquiterpenoid from Copaiba Oil.

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.

Patients' Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia.

The use of traditional medicinal plants in Saudi Arabia stems mainly from consumers' belief in prophetic medicine. This study was conducted to explore changes in patients' use of dietary or herbal supplements among individuals infected with COVID-19 before and during infection and the association between herbal or dietary supplements and hospitalization. A cross-sectional, questionnaire-based study was conducted enrolling symptomatic patients who had recently recovered from COVID-19. Data were collected through phone interviews, and McNemar's test was used to investigate changes to consumption of dietary or herbal supplements before and during infection. Multivariable logistic regression was used to investigate the association between supplements use during patients' infection and hospitalization. A total of 738 patients were included in this study, of whom 32.1% required hospitalization. About 57% of participants were male with a mean age of 36.5 (±11.9) years. The use of lemon/orange, honey, ginger, vitamin C, and black seed among participants significantly increased during their infection. In contrast, patients using anise, peppermint, and coffee peel before their infection were more likely to stop using them during their infection. In addition, using lemon/orange (p < 0.0001), honey (p = 0.0002), ginger (p = 0.0053), vitamin C (p = 0.0006), black seed (p < 0.0001), peppermint (p = 0.0027), costus (p = 0.0095), and turmeric (p = 0.0012) was significantly higher among nonhospitalized patients than hospitalized ones. However, in the multivariable logistic regression, only use of vitamin C (OR = 0.51; 95% CI 0.33-0.79), peppermint (OR = 0.53; 95% CI 0.31-0.90), and lemon/orange (OR = 0.54; 95% CI 0.33-0.88) was associated with significantly lower odds of hospitalization. The study reveals that patients' consumption of dietary or herbal supplements changed in response to their COVID-19 infection, with hospitalized patients having a lower likelihood of using these supplements. Because some supplements were associated with lower odds of hospitalization, these supplements or their bioactive components should be further investigated as feasible options for COVID-19 treatment.

Deeper Insights on Cnesmone javanica Blume Leaves Extract: Chemical Profiles, Biological Attributes, Network Pharmacology and Molecular Docking.

This study assessed the anxiolytic and antidepressant activities of a methanol leaves extract of Cnesmone javanica (CV) in Swiss albino mice. The study found a significant increase in the percentage of time spent in the open arms of an elevated plus maze and in the incidence of head dipping in hole-board tests following the administration of 400 mg/kg of CV or 1 mg/kg diazepam. Moreover, a significant (p < 0.001) dose-dependent reduction was observed in the immobility time following CV (200 and 400 mg/kg) and fluoxetine (20 mg/kg) administration for forced swimming and tail suspension tests. Gas chromatography-mass spectroscopy (GC-MS) analysis identified 62 compounds in CV, consisting primarily of phenols, terpenoids, esters, and other organic compounds. A molecular docking study was performed to assess the anxiolytic and antidepressant effects of 45 selected compounds against human serotonin transporter and potassium channels receptors. Network pharmacology was performed to predict the pathways involved in these neuropharmacological effects. Overall, CV demonstrated significant and dose-dependent anxiolytic and antidepressant effects due to the presence of several bioactive phytoconstituents, which should be further explored using more advanced and in-depth mechanistic research.