Magterpenes A-C: Three Meroterpenoids with an Unprecedented 6/6/6/6/6 Polycyclic Skeleton Extracted from Magnolia officinalis Rehd. et Wils.

Magterpenes A-C (1-3), three unprecedented meroterpenoids featuring a unique 6/6/6/6/6 polycyclic skeleton, were isolated from the ethanol extract of Magnolia officinalis Rehd. et Wils. The compounds were obtained as racemic mixtures that were completely resolved through chiral columns. Their structures were elucidated by extensive analyses of one-dimensional (1D) and 2D nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, chemical calculations of 1H/13C NMR, and electronic circular dichroism calculations. The compounds were constructed via two Diels-Alder reactions in the proposed biosynthetic pathway. All isolates were evaluated for their nephroprotective and hepatoprotective activities. The results demonstrated that (+)-1 and (-)-1 possessed promising nephroprotective activities in a dose-dependent manner, while (-)-2 and (+)-3 exhibited moderate hepatoprotective activities.

Discovery and evaluation of novel spiroheterocyclic protective agents via a SIRT1 upregulation mechanism in cisplatin-induced premature ovarian failure.

Currently, no effective treatment exists for premature ovarian failure (POF). To obtain compounds with protective effects against POF, we aimed to design and synthesize a series of spiroheterocyclic protective agents with a focus on minimizing toxicity while enhancing their protective effect against cisplatin-induced POF. This was achieved through systematic modifications of Michael receptors and linkers within the molecular structure of 1,5-diphenylpenta-1,4-dien-3-one analogs. To assess the cytotoxicity and activity of these compounds, we constructed quantitative conformational relationship models using an artificial intelligence random forest algorithm, resulting in R2 values exceeding 0.87. Among these compounds, j2 exhibited optimal protective activity. It significantly increased the survival of cisplatin-injured ovarian granulosa KGN cells, improved post-injury cell morphology, reduced apoptosis, and enhanced cellular estradiol (E2) levels. Subsequent investigations revealed that j2 may exert its protective effect via a novel mechanism involving the activation of the SIRT1/AKT signal pathway. Furthermore, in cisplatin-injured POF in rats, j2 was effective in increasing body, ovarian, and uterine weights, elevating the number of follicles at all levels in the ovary, improving ovarian and uterine structures, and increasing serum E2 levels in rats with cisplatin-injured POF. In conclusion, this study introduces a promising compound j2 and a novel target SIRT1 with substantial protective activity against cisplatin-induced POF.

LC-QTOF-MS/MS metabolic profiling and hepatoprotective effects of Litsea monopetala bark methanol extract against liver injury in rats and HepG2 cells.

Fresh stem bark decoction of Litsea monopetala has been practiced for the treatment of jaundice and other liver disorders by the tribal communities of Thakht-e-Sulaiman hills from West Pakistan. As per the folkloric claim, this study aims to identify the phytoconstituents and evaluate the hepatoprotective action of stem bark methanol extract of L. monopetala (LMME). The in-vitro hepatoprotective effect of L. monopetala was performed by H2O2-induced toxicity in the HepG2 cell line and in-vivo by cclt;sub>4-induced hepatotoxicity in Wistar albino rats taking Silymarin as standard drug. Phytoconstituents were identified using LC-QTOF-MS analysis followed by in-silico docking and validation. Molecular docking interactions between identified compounds of L. monopetala and two target proteins, namely 1VJY and 5HYK were presented. In this study, treatment with LMME at 100 µg/mL showed 67.73 % cell viability as compared to H2O2 (100 µM) treated alone i.e., 18.55 % in the HepG2 cell line. In-vivo treatment of LMME reversed the altered serum biochemical parameters and reduced the inflammatory response similar to that of the Silymarin-treated group supported by histopathological investigation. This research reveals that L. monopetala is a rich source of flavonoids and phenols which supports its hepatoprotective effects and is proposed for its usage as a promising hepatoprotective agent after controlled trials.

Minor Hydroxylated Triterpenoids Produced in Engineered Yeast by the Enzymes OSC and CYP716s from the Plant Enkianthus chinensis and Their Anti-Inflammatory and Hepatoprotective Activities.

Triterpenoids are a type of specialized metabolites that exhibit a wide range of biological activities. However, the availability of some minor triterpenoids in nature is limited, which has hindered our understanding of their pharmacological potential. To overcome this limitation, heterologous biosynthesis of triterpenoids in yeast has emerged as a promising and time-efficient production platform for obtaining these minor compounds. In this study, we analyzed the transcriptomic data of Enkianthus chinensis to identify one oxidosqualene cyclase (EcOSC) gene and four CYP716s. Through heterologous expression of these genes in yeast, nine natural pentacyclic triterpenoids, including three skeleton products (1-3) produced by one multifunctional OSC and six minor oxidation products (4-9) catalyzed by CYP716s, were obtained. Of note, we discovered that CYP716E60 could oxidize ursane-type and oleanane-type triterpenoids to produce 6ß-OH derivatives, marking the first confirmed C-6ß hydroxylation in an ursuane-type triterpenoid. Compound 9 showed moderate inhibitory activity against NO production and dose-dependently reduced IL-1ß and IL-6 production at the transcriptional and protein levels. Compounds 1, 2, 8, and 9 exhibited moderate hepatoprotective activity with the survival rates of HepG2 cells from 61% to 68% at 10 µM.

Discovery of novel natural cardiomyocyte protectants from a toxigenic fungus Stachybotrys chartarum.

Stachybatranones A-F (1a/1b and 2-6) and three known analogues, namely methylatranones A and B (7 and 8) and atranone B (9), were isolated and identified from a toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated via the extensive spectroscopic data, comparison of the experimental electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analyses. Structurally, compounds 2-6 belonged to a rare class of C-alkylated dolabellanes, featuring a unique five-membered hemiketal ring and a γ-butyrolactone moiety both fused to an 11-membered carbocyclic system, while compound 1 (1a/1b) represented the first example of a 5-11-6-fused atranone possessing a 2,3-butanediol moiety. The cardiomyocyte protective activity assay revealed that compounds 1-9 ameliorated cold ischemic injury at 24 h post cold ischemia (CI), with compounds 1 and 4 acting in a dose-dependent manner. Moreover, compound 1 prevented cold ischemia induced dephosphorylation of PI3K and AKT acting in a dose-dependent manner. In this study, a new class of natural products were found to protect cardiomyocytes against cold ischemic injury, providing a potential option for the development of novel cardioprotectants in heart transplant medicine.

Novel lignans from Syringa pinnatifolia and protective effect against H2O2-induced oxidative injury through regulating the expression of Nrf2/HO-1 in H9c2 cells.

Phytochemical analysis of the peeled stems of Syringa pinnatifolia Hemsl. led to the discovery of 13 undescribed lignans, namely helanols A and B (1 and 2) and alashanenols W-G1 (3-13), as well as four known analogues, of which helanols A and B were lignans with novel skeleton of α-ß' linkage. The structures were unambiguously established by extensive spectroscopic analyses, NMR calculations, ECD calculations, and single crystal X-ray crystallography. Five lignans (1, 2, 5, 11 and 13) exhibited a moderate protective effect against H2O2-induced oxidative injuries in H9c2 cells with the protective rates of 11.3-20.6 % at the concentration of 0.3-20 µM, while the positive control quercetin showed protective rates of 58.7 % at 10 µM. Further mechanism investigation suggested that 1 and 2 exerted the protective effect by regulating the expression of Nrf2/HO-1.

Protective effects of baicalin against phenylarsine oxide-induced cytotoxicity in human skin keratinocytes.

Phenylarsine oxide (PAO) is a known environmental pollutant and skin keratinocytes are most seriously affected. Baicalin (BCN) was reported to have antioxidant and anti-inflammatory effects, but its protective effect against PAO toxicity is unknown. This study aimed at exploring whether baicalin can reverse the toxicity of human epidermal keratinocytes that are subjected to PAO exposure and underlying mechanisms. In silico analysis from a publicly accessible HaCaT cell transcriptome dataset exposed to chronic Arsenic showed significant differential expression of several genes, including the genes related to DNA replication. Later, we performed in vitro experiments, in which HaCaT cells were exposed to PAO (500 nM) in the existence of BCN (10-50 µM). Treatment of PAO alone induces the JNK, p38 and caspase-3 activation, which were engaged in the apoptosis induction, while the activity of AKT was significantly inhibited, which was engaged in the suppression of apoptosis. PAO suppressed SIRT3 expression and induced intracellular reactive oxygen species (ROS), causing a marked reduce in cell viability and apoptosis. However, BCN treatment restored the PAO-induced suppression of SIRT3 and AKT expression, reduced intracellular ROS generation, and markedly suppressed both caspase-3 activation and apoptosis induction. However, the protective effect of BCN was significantly attenuated after pretreatment with nicotinamide, an inhibitor of SIRT3. These findings indicate that BCN protects against cell death induced by PAO via inhibiting excessive intracellular ROS generation via restoring SIRT3 activity and reactivating downstream AKT pathway. In this study, we firstly shown that BCN is an efficient drug to prevent PAO-induced skin cytotoxicity, and these findings need to be confirmed by in vivo and clinical investigations.

Defining the mechanisms behind the hepatoprotective properties of curcumin.

As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered.

Stem-Cell-Regenerative and Protective Effects of Squid (Symplectoteuthis oualaniensis) Skin Collagen Peptides against H2O2-Induced Fibroblast Injury.

Recently, there has been a growing interest in collagen peptides derived from marine sources for their notable ability to protect skin cells against apoptosis induced by oxidants. Therefore, the current study aimed to investigate the fundamental properties of collagen peptides, including their physicochemical, thermal, structural, stem-cell-regenerative, and skin-cell-protective effects, in comparison to commercial collagen peptides. The acid-soluble (ASC) and pepsin-soluble (PSC) collagens exhibited three distinct bands on SDS-PAGE, namely α (α1 and α2), ß, and γ chains, confirming a type I pattern. The thermal profiles obtained from TG and DSC analyses confirmed the denaturation of PSC and ASC at temperatures ranging from 51.94 to 56.4 °C and from 52.07 to 56.53 °C, respectively. The purified collagen peptides were analyzed using SDS-PAGE and MALDI-TOF mass spectrometry, revealing a mass range of 900-15,000 Da. Furthermore, the de novo peptide sequence analysis confirmed the presence of the Gly-X-Y repeating sequence in collagen peptides. Collagen peptide treatments significantly enhanced HFF-1 cell proliferation and migration compared to the control group. ELISA results confirmed the potential interactions between collagen peptides and HFF-1 cells through α2ß1, α10ß1, and α11ß1 integrin receptors. Notably, collagen peptide treatment effectively restored the proliferation of HFF-1 cells damaged by H2O2. Consequently, the advantageous characteristics of squid skin collagen peptides highlight their promising role in regenerative medicine.

Assessment of Silver Nanoparticles Derived from Brown Algae Sargassum vulgare: Insight into Antioxidants, Anticancer, Antibacterial and Hepatoprotective Effect.

Algae are used as safe materials to fabricate novel nanoparticles to treat some diseases. Marine brown alga Sargassum vulgare are used to fabricate silver nanoparticles (Sv/Ag-NPs). The characterization of Sv/Ag-NPs was determined by TEM, EDX, Zeta potential, XRD, and UV spectroscopy. The Sv/Ag-NPs were investigated as antioxidant, anticancer, and antibacterial activities against Gram-positive bacteria Bacillus mojavensis PP400982, Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. The activity of the Sv/Ag-NPs was evaluated as hepatoprotective in vitro in comparison with silymarin. The UV-visible spectrum of Sv/Ag-NPs appeared at 442 nm; the size of Sv/Ag-NPs is in range between 6.90 to 16.97 nm, and spherical in shape. Different concentrations of Sv/Ag-NPs possessed antioxidant, anticancer activities against (HepG-2), colon carcinoma (HCT-116), cervical carcinoma (HeLa), and prostate carcinoma (PC-3) with IC50 50.46, 45.84, 78.42, and 100.39 µg/mL, respectively. The Sv/Ag-NPs induced the cell viability of Hep G2 cells and hepatocytes treated with carbon tetrachloride. The Sv/Ag-NPs exhibited antibacterial activities against Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. This study strongly suggests the silver nanoparticles derived from Sargassum vulgare showed potential hepato-protective effect against carbon tetrachloride-induced liver cells, and could be used as anticancer and antibacterial activities.

Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen.

Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.

Hepatoprotective Lignan Glycosides from the Leaves and Stems of Symplocos cochinchinensis (Lour.) S. Moore.

This study investigates Symplocos cochinchinensis (Lour.) S. Moore leaves and stems, commonly known as Symplocos, a plant indigenous to Asia renowned for its traditional use in holistic medicine. A comprehensive phytochemical analysis of S. cochinchinensis led to the isolation of two new lignans, namely symplolignans A and B (1 and 2) along with eleven known lignan glucosides: nortrachelogenin 4-O-ß-D-glucopyranoside (3), nortracheloside (4), matairesinol 4-O-ß-D-glucopyranoside (5), lariciresinol 4'-O-ß-D-glucopyranoside (6), balanophonin 4-O-ß-D-glucopyranoside (7), dehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (8), dehydrodiconiferyl alcohol γ'-O-ß-D-glucopyranoside (9), 3-(ß-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofura (10), and pinoresinol 4'-O-ß-D-glucopyranoside (11). Their chemical structures were elucidated using 1D- and 2D-NMR, mass spectrometry, and their spectroscopic data were compared with those reported in literatures. Furthermore, all compounds were evaluated for their hepatoprotective effects using the Resazurin reduction assay in HepG2 hepatocellular carcinoma cells. Compounds 1, 5, 7, and 8 exhibited notable hepatoprotective efficacy, with cell viability ranging from 105.0±2.6 to 109.2±3.3 at a concentration of 10 µM. This research highlights the therapeutic potential of these compounds and enhanced to the understanding of lignans and neolignans in liver cell proliferation.

Protective Effect of a Isothiazolinone Derivative on Acute Lung Injury by Regulating PI3K-AKT Signaling Pathway.

Acute lung injury (ALI) is a prevalent organ injury in sepsis, characterized by an inflammatory reactive disorder. Both the incidence and mortality rates of ALI have been steadily increasing. Isothiazolinone derivatives have displayed anti-inflammatory activity and have shown effectiveness in treating pneumonia. The objective of the study is to assess the effects and mechanisms of the isothiazolinone derivative 4-benzoyl-2-butyl-5-(ethylsulfinyl)isothiazol-3(2H)-one (C6) on sepsis-induced ALI.The analysis of biological function and signal pathway enrichment demonstrated that C6 primarily exhibited anti-inflammatory effects. Administration of different doses of C6 through intraperitoneal injection significantly improved the survival rate, body temperature, and body mass of mice with ALI induced by cecal ligation and puncture (CLP). Additionally, it mitigated lung tissue injury, pulmonary edema, lung permeability, inflammatory cell infiltration, apoptosis, and the expression of inflammatory cytokines. Network targeting analysis and experimental validation in mouse leukemia cells of monocyte macrophage (RAW264.7) cells and CLP-induced ALI mice revealed that the anti-inflammatory effect of C6 was mediated by the inhibition of the phosphatidylinositol 3 kinase -protein kinase B (PI3K-AKT) signaling pathway. The research suggest that C6 has protective effects against ALI by inhibiting the PI3K-AKT signaling pathway. This information could be valuable in developing potential treatments for ALI.

Protective Effects of Tunisian Orange Co-Product Extract and Oleuropein-Hesperidin Combination on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.

Urolithin a Partially Protects against Oxidative Damage Induced for Microcistyn-lr in C6 Cells.

Microcystin-LR (MIC-LR) is a toxin which the mechanism of intoxication involves oxidative stress. Urolithin A (URO-A) is a metabolic product from the colonic fermentation of ellagic acid with antioxidant potential. This study aimed to evaluate the putative protective effect of URO-A against MIC-LR toxicity in C6 cells. C6 cells were incubated with MIC-LR (1 and 10 µM) and/or URO-A (3, 30, 60 and 100 µM) for 24 h. MIC-LR induced reactive species (RS) generation, depletion of total thiol (SH) groups, and survival loss when compared with the control group. Also, at 10 µM, MIC-LR induced CAT activity inhibition. URO-A caused CAT activity inhibition and showed a trend to increase RS generation (60 and 100 µM) per se. URO-A at 3 µM completely attenuated the RS generation and the impairment in SH groups caused by MIC-LR. Our results demonstrated that URO-A might offer a protective effect against toxicity caused by MIC-LR in glial cells by restoring the levels of RS and thiol groups.

Phytochemical Analysis, and Antioxidant and Hepatoprotective Activities of Chamaerops humilis L. Leaves; A Focus on Xanthine Oxidase.

Chamaerops humilis L. is clumping palm of the family Arecaceae with promising health-promoting effects. Parts of this species are utilized as food and employed in folk medicine to treat several disorders. This study investigated the phytochemical constituents of C. humilis leaves and their antioxidant and xanthine oxidase (XO) inhibitory activities in vitro and in vivo in acetaminophen (APAP)-induced hepatotoxicity in rats. The chemical structure of the isolated phytochemicals was determined using data obtained from UV, MS, IR, and 1H-, 13C-NMR spectroscopic tools as well as comparison with authentic markers. Eleven compounds, including tricin 7-O-ß-rutinoside, vicenin, tricin, astragalin, borassoside D, pregnane-3,5,6,16-tetrol, oleanolic acid, ß-sitosterol and campesterol were isolated from C. humilis ethanolic extract (CHEE). CHEE and the butanol, n-hexane, and dichloromethane fractions exhibited in vitro radical scavenging and XO inhibitory efficacies. The computational findings revealed the tendency of the isolated compounds towards the active site of XO. In vivo, CHEE ameliorated liver function markers and prevented tissue injury induced by APAP in rats. CHEE suppressed hepatic XO, decreased serum uric acid and liver malondialdehyde (MDA), and enhanced reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in APAP-treated rats. CHEE ameliorated serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in APAP-treated rats. Thus, C. humilis is rich in beneficial phytochemicals that possess binding affinity towards XO. C. humilis exhibited potent in vitro antioxidant and XO inhibitory activities, and prevented APAP hepatotoxicity by attenuating tissue injury, oxidative stress and inflammation.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms.

Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.

Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a ß-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-ßRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT-eNOS Pathway.

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

BACKGROUND: Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. METHODS: Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. RESULTS: AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-ß, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-ß, and MMP9 gene expression in renal tissues compared to the AlCl3 group. CONCLUSION: SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.