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Background: Traditional Chinese medicine suggests that Radix Achyranthis Bidentatae nourishes and protects the kidneys, the effect of which is enhanced following a salt treatment. Raw and salt-processed Achyranthes bidentata are produced via different processing techniques from the same crude Achyranthes root. The anti-inflammatory and immunomodulatory properties of this plant have been verified earlier. However, there is a scarcity of experimental evidence for the renal-protective effects., Aim: The purpose of present study is to compare the protective effects of raw and salt-processed Achyranthes on lipopolysaccharide (LPS) - induced acute kidney injury in mice and chemically characterize their extracts., Method: The monomer components of raw and salt-processed Achyranthes extracts were analyzed using high performance liquid chromatography (HPLC). The aggregation and distribution of 2-Deoxy-D-glucose (2-DG) near infrared fluorescence probe in mice was examined with a small animal imaging systems. The pathological and morphological changes of kidneys were observed by H&E staining, and the serum urea nitrogen (BUN) and serum creatinine (Scr) levels were used to evaluate the renal function. The levels of cytokines in serum were detected by cytometric bead array. Flow cytometry assay was performed to assess the apoptosis and reactive oxygen species (ROS) in the kidney cells, and cell surface marker expression including CD45 + , F4/80 + , and Ly-6G + . The estrogenic activities of the raw and salt-processed Achyranthes were observed by uterine weight gain test in sexually immature mice. Western blot was used to detect the protein expression levels in the kidney., Results: Chemical analysis showed that the salt-processed Achyranthes contained more ginsenoside Ro and chikusetsusaponin Ⅳa than the raw Achyranthes, but there was no difference in the contents of β-ecdysterone, 25R-inokosterone, and 25S-inokosterone.in vivo near-infrared fluorescence imaging showed a significant reduced inflammation in the AKI mice. Histological studies showed that the raw and salt-processed Achyranthes markedly decreased the inflammatory infiltration, swelling and vacuolar degeneration in renal tissues and the Scr and BUN. Importantly, the raw and salt-processed Achyranthes extracts demonstrated different degrees of inhibition on the LPS-induced AKI, with salt-processed Achyranthes showing better inhibition. Results of flow cytometry showed a significant inhibition of IFN-γ, TNF-α, and IL-2, and promoted IL-10, along with reduced macrophages (CD45 + F4/80+), neutrophils (CD45+ Ly-6G+) and phagocytes. Furthermore, the extracts reduced the accumulation of ROS and apoptosis in the kidney, and also regulated the expression of apoptosis marker proteins TLR4, Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9 levels. Notably, they increased ERα, ERβ, and GPR30 in the renal tissues of AKI mice and LPS non-treated mice. In the subsequent experiments, it was found that the raw and salt-processed Achyranthes extracts increased the uterine coefficient in sexually immature mice, improved the LPS-induced decrease in NRK52e cell viability, and reduced the apoptosis, which could be antagonized by ICI182, 780 (estrogen receptor-unspecific antagonist, Faslodex)., Conclusions: The renal-protective effect of raw and salt-processed Achyranthes was exhibited through antiapoptotic and antioxidant mechanisms via an estrogen-like pathway, along with a modulation of the inflammatory response by regulating immune cells. Ginsenoside Ro and Chikusetsu saponin IVa were found to be the key factors to enhance the protective effect of salt-processed Achyranthes., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Alzheimer's disease (AD) is a common chronic neurodegenerative disease in older people, and there is no specific treatment that can stop or reverse its progression. Neobavaisoflavone (NBIF) is a flavonoid that has been shown to have neuroprotective effects, but its role in AD has not been revealed. The present study investigated the role and mechanism of NBIF on Aβ25‐35‐induced brain injury. Methods: In this experiment, the AD mouse model was established by injection of Aβ25‐35 peptides (200 μM, icv), and Donepezil (Don, 10 mg/kg/days), NBIF‐L (15 mg/kg/days), and NBIF‐H (30 mg/kg/days) were administered orally for 4 weeks. Learning memory, hippocampal pathological changes, pathological markers, apoptosis, oxidative stress, inflammation, immune cells were measured in mice. Network pharmacology combined with the GEO database led to the identification of SIRT1, a key target for NBIF intervention in AD, and levels of SIRT1, p‐STAT3 and FOXO1 were measured. In addition, the antagonistic activity of SIRT1 transfection silencing against NBIF in Aβ25‐35‐induced in N9 cells and N2a‐APP69 cells was investigated to assess whether the effects caused by NBIF were mediated by SIRT1. Results: The results showed that NBIF ameliorated learning memory and hippocampal neuronal damage, reduced pathological markers, apoptosis, oxidative stress and neuroinflammation, and modulated immune cells. SIRT1 is a key target for NBIF intervention in AD, and NBIF upregulates SIRT1 and reduces the expression levels of p‐STAT3 and FOXO1. Furthermore, silencing SIRT1 effectively reduced the protective effect of NBIF on Aβ25‐35‐induced N9 cells and N2a‐APP69 cells, which indicated that the protective effect of NBIF on AD is related to SIRT1. Conclusions: NBIF ameliorated Aβ25‐35‐induced brain injury by inhibiting apoptosis, oxidative stress, and neuroinflammation, which may be mediated through SIRT1 signaling. These findings provide a rationale for NBIF in the treatment of AD and help facilitate the development of clinical therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a frequent complication of sepsis with hallmarks including inflammation and oxidative stress. A large amount of oleanolic acid derivatives (TO) have been isolated from Gardenia jasminoides var. radicans, a traditional Chinese medicine with anti-inflammatory efficacy; thus, the aim of the present study was to evaluate the protective effects of TO on injury in a murine model of endotoxemic AKI. Kidney function, inflammation, oxidative stress, apoptosis, white blood cell count, TLR4/NF-κB/NLRP3 pathway involvement and metabolic profiling of the serum were evaluated. The results show that TO significantly ameliorated renal function in mice with LPS-induced AKI; 2-deoxy- D -glucose (2-DG) optical probe imaging indicated that TO markedly reduced the levels of inflammation; flow cytometry demonstrated that TO had an excellent antioxidant effect, regulating immune cells; Western blotting indicated that TO inhibited the TLR4/NF-κB/NLRP3 signaling pathway; and metabolic profiling of the serum also demonstrated the protective effects of TO on injury in a murine model of endotoxemic AKI. In summary, TO renoprotection involves the attenuation of LPS-induced renal inflammation and oxidative stress, which may be mediated via inhibition of the TLR4/NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a syndrome characterized by a systemic inflammatory response. Arbutin (Ar) is an active natural product known for its bactericidal and anti-inflammatory effects. Many studies have reported the diverse pharmacological actions of Ar, but there is no relevant research on the effect of Ar on lipopolysaccharide (LPS)-induced myocardial injury. Objective: The purpose of this study was to investigate the effect of Ar on LPS-induced myocardial injury and its underlying mechanisms. Materials and Methods: The levels of tumor necrosis factor alpha, interleukin 6, cardiac troponin-I, and procalcitonin were detected by ELISA. The levels of phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated extracellular regulated protein kinase (p-ERK), and phosphorylated p38 (p-p38) proteins were detected by flow cytometry using Cytometric Bead Array. Western blot was used to detect the expression of autophagy-related and estrogen receptor (ER)-associated proteins. Levels of the oxidative stress-related markers were detected by the cuvette assay. Results: The levels of the inflammatory factors, LC3B, malondialdehyde, p-JNK, and p-p38 were increased in LPS-treated rats, while the ERK, total superoxide dismutase, glutathione peroxidase, p62, and ER-associated proteins were decreased. These effects could be effectively reversed by Ar, which could be blocked by ER antagonist ICI182780. Our previous study found Ar to possess an estrogen-like activity. Conclusion: Ar inhibits the oxidative stress and autophagy and offers protection from the LPS-induced myocardial injury via the ER pathway. [ABSTRACT FROM AUTHOR]

Background: Rehmannia Glutinosa Libosch. is applied for the treatment of renal and inflammatory-related diseases, and oleic acid (OA) is a compound isolated from Rehmannia Glutinosa Libosch.. Unfortunately, the pharmacological activity of OA on LPS treated acute kidney injury (AKI) has not been investigated.Aims: The research is aiming to probe the activities of OA on LPS-induced AKI.Methods: Information of OA effect on AKI were from network pharmacology. H&E staining, creatinine (CRE) and urea nitrogen (UN) were performed to evaluate the activities of OA on kidney function. Inflammatory factors in serum were measured by cytometric bead array. Increased ratio of reactive oxygen species (ROS) in kidney and immune cells in the peripheral blood were determined by flow cytometry (FCM). PPAR-γ, MAPK and apoptotic signaling pathways were measured by Western blot. Then, a metabolomics approach was utilized to investigate OA's response to AKI. The role of salirasib (FTS, Ras inhibitor) in OA acted on ROS, Ca2+, MMP and Ras signaling pathway in LPS treated NRK-52e cells were investigated by FCM and In-cell western.Results: It is proved that OA effetively ameliorated renal function, alleviated inflammatory response and oxidative stress, and transformed apoptotic, MAPK and PPAR-γ signaling pathways in mice with AKI, regulated phenylalanine metabolism, purine metabolism, sphingolipid metabolism, taurine and hypotaurine metabolism, moreover, the role of OA in injury of NRK-52e was blocked by FTS.Conclusion: In a word, OA could alleviate AKI by restraining inflammation and oxidative stress via regulating the Ras/MAPKs/PPAR-γ signaling pathway, phenylalanine metabolism, purine metabolism, sphingolipid metabolism and taurine and hypotaurine metabolism, which might be a useful strategy for treating AKI. [ABSTRACT FROM AUTHOR]

• Camellia oil had a protective effect on AKI by inhibiting TLR4 signaling. • Oleic acid was the most abundant component of camellia oil, which was able to bind to the TLR4−MD-2 complex and inhibit the TLR4 signaling cascades. This was likely the material basis for the protective effect of camellia oil. • These data provide a further pharmacological basis for the clinical application of camellia oil to prevent AKI. Camellia oil, used as both a traditional Chinese medicine and a nutritious food, is an excellent candidate for arresting acute kidney injury (AKI) in sepsis. The present study aimed to provide further evidence for the clinical application of camellia oil to prevent AKI by further delineating the involvement of the TLR4 signaling cascades in its effects. Firstly, significant physiological indices were examined to assess the model and the intervention efficacy of camellia oil. The effect of camellia oil on the NLRP3 pathway and three key transcription factors of the TLR4 signaling cascades, NF-κB, AP-1 and IRF3, were also investigated in LPS-induced AKI rats using the multiplex biometric immunoassay. Furthermore, gas chromatography-mass spectrometry (GC–MS) was used to analyze the composition of camellia oil, and molecular docking was employed to evaluate the interaction between the most abundant component of camellia oil and the TLR4−MD-2 complex. The integrated results demonstrate that camellia oil had a protective effect on AKI by inhibiting TLR4 signaling. Oleic acid was found to be the most abundant component of camellia oil, which was able to bind to the TLR4−MD-2 complex and inhibit the TLR4 signaling cascades. This was likely the material basis for the protective effect of camellia oil. These data provide a further pharmacological basis for the clinical application of camellia oil to prevent AKI and help to understand the herbal function and "homology of medicine and food". [ABSTRACT FROM AUTHOR]

The identification of noninvasive volatile biomarkers for lung cancer is a significant clinical challenge. Through in vitro studies, the recognition of altered metabolism in cell volatile organic compound (VOC) emitting profile, along with the occurrence of oncogenesis, provides insight into the biochemical pathways involved in the production and metabolism of lung cancer volatile biomarkers. In this research, for the first time, a comprehensive comparative analysis of the volatile metabolites in NSCLS cells (A549), SCLC cells (H446), lung normal cells (BEAS-2B), as well as metabolites in both the oxidative stress (OS) group and control group. Specifically, the combination of eleven VOCs, including n -dodecane, acetaldehyde, isopropylbenzene, p -ethyltoluene and cis -1,3-dichloropropene, exhibited potential as volatile biomarkers for lung cancer originating from two different histological sources. Furthermore, the screening process in A549 cell lines resulted in the identification of three exclusive biomarkers, isopropylbenzene, formaldehyde and bromoform. Similarly, the exclusive biomarkers 1,2,4-trimethylbenzene, p -ethyltoluene, and cis -1,3-dichloropropene were present in the H446 cell line. Additionally, significant changes in trans -2-pentene, acetaldehyde, 1,2,4-trimethylbenzene, and bromoform were observed, indicating a strong association with OS. These findings highlight the potential of volatile biomarkers profiling as a means of noninvasive identification for lung cancer diagnosis. [Display omitted] •The VOCs generated through cellular metabolism were compared across cell lines. •Cell VOCs detection reflects their metabolism and helps volatile biomarkers screening. •Potential breath VOC biomarkers were identified for A549 and H446 cell lines. •Four VOCs of the cancer cell metabolites are related to the oxidative stress reaction. •Potential metabolic mechanisms of certain VOCs with significant differences were verified. [ABSTRACT FROM AUTHOR]

Background. Duzhong Butiansu (DZBTS) prescription contains many traditional Chinese medicines and has been shown to have a curative effect on male fertility. However, the efficacy and mechanism of DZBTS in the treatment of male infertility induced by heat stress have not been reported. The aim of the present study is to elucidate the effect and mechanism of DZBTS on spermatogenic function of a heat stress model in rats. Methods. Male Wistar rats (280–320 g) were given different doses of DZBTS (0.4853 g/kg/d or 0.9707 g/kg/d), Shengjing capsule (0.56 g/kg/d), or double distilled water for 15 days. A 43°C hot water bath for 30 minutes was used to stimulate the testis of rats. Sperm count, sperm motility, the organ index of kidney and gonadal organs, serum sex hormone levels, and serum oxidising reaction index were measured. Haematoxylin and eosin (HE) staining was used to observe the morphology of the testis and kidney. The expression of Hsp70 in testes was observed by immunofluorescence. The changes in heat stress, reproductive-related protein, and mRNA were measured by western blot assay and RT-qPCR. Results. Heat stress downregulated the levels of sex hormone (P < 0.05 or P < 0.01) and its receptor androgen receptor (AR) protein expression and mRNA (P < 0.01) in rats. Meanwhile, heat stress downregulated the levels of CAMP-responsive element-binding (CREB1) protein and mRNA (P < 0.01), which are involved with spermatogenesis. Heat stress also decreased the oxidative damage index. Furthermore, Hsp70 and the heat shock transcription factor 1 (HSF1) protein pathway and mRNA level were overactivated (P < 0.05 or P < 0.01). Finally, the organ coefficients of the kidney and gonadal organs of rats were decreased. The sperm concentration and motility also decreased significantly (P < 0.01). DZBTS could recover these changes induced by heat stress. Conclusions. Our results for the first time have found that DZBTS can improve spermatogenesis disorder in a heat stress model in rats, which may be mainly by regulating AR, sperm regulatory protein CREB1, and the HSF/Hsp70 signaling pathway to decrease oxidative stress. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive disease with a long duration and complicated pathogenesis. Thymidine (Thy) and 2′-deoxyuridine (2′-De) are pyrimidines nucleotides that are associated with nervous system diseases. However, it remains unclear whether Thy and 2′-De exert neuroprotective effects in AD. Therefore, this study was conducted to explore the interventional effects and mechanisms of Thy and 2′-De on the Aβ 25-35 -induced brain injury. Donepezil (Do, 10 mg/kg/d), Thy (20 mg/kg/d), and 2′-De (20 mg/kg/d) were administered for 4 weeks after the injection of Aβ 25-35 peptides (200 μM, i.c.v.) to mice. UPLC-MS/MS method was performed to quantify Thy and 2′-De in the hippocampus of mice brain. The cognition ability, neuronal and mitochondria damage, and levels of Aβ 1-42 /Aβ 1-40 , p -Tau, Na+ K+-ATPase, apoptosis, oxidative stress, immune cells, and Iba 1+ were measured in Aβ 25-35 -induced mice. The oxygen consumption (OCR) and extracellular acidification rate (ECAR) were measured using a seahorse analyzer in Aβ 25-35 -induced N9 cells. Moreover, 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was added to explore the mechanisms underlying the effects of Thy and 2′-De on Aβ 25-35 -induced N9 cells. The expression of Iba 1+ and levels of CD11b+ and reactive oxygen species (ROS) were measured after treatment with Thy (5 μM) and 2′-De (10 μM) against 2-DG (5 mM) in Aβ 25-35 -induced N9 cells. The results suggested that Do, Thy, and 2′-De improved the cognition ability, attenuated the damage to hippocampus and mitochondria, downregulated the levels of Aβ 1-42 /Aβ 1-40 , p -Tau, Na+ K+-ATPase, apoptosis, oxidative stress, and Iba 1+, and regulated the immune response induced by Aβ 25-35 against the brain injury. Furthermore, Do, Thy, and 2′-De increased ATP production and inhibited glycolysis in Aβ 25-35 -induced N9 cells. Moreover, 2-DG enhanced the effects of drugs, reduced microglial activation, and attenuated oxidative stress to interfere with Aβ 25-35 -induced N9 cells. In conclusion, Thy and 2′-De reduced microglial activation and improved oxidative stress damage by modulating glycolytic metabolism on the Aβ 25-35 -induced brain injury. • Thymidine and 2′-deoxyuridine have protective effects against cognitive and memory impairment in the Aβ 25-35 -induced AD mice model • Thymidine and 2′-deoxyuridine have anti-oxidant anti-apoptosis effects by reducing mitochondrial damage in the Aβ 25-35 -induced AD mice model • Thymidine and 2′-deoxyuridine reduce microglial activation and oxidative stress damage by modulating glycolytic metabolism to interfere with the Aβ 25-35 -induced N9 cells [ABSTRACT FROM AUTHOR]

[Display omitted] The root of Rehmannia glutinosa (R. glutinosa) is commonly used in various traditional Chinese herbal formulae to ameliorate nephropathy; however, little is known about its active component(s) and mechanisms. In the present study, we examined the protective effect and potential mechanism of rehmapicrogenin, a monomeric compound extracted from R. glutinosa , against Adriamycin (ADR)-induced nephropathy (AN) in vivo and in vitro. In this study, an ADR-induced kidney injury model was employed to investigate the nephroprotective effects of rehmapicrogenin in mice. In vivo , ELISA kits, flow cytometry, haematoxylin-eosin staining, immunofluorescence techniques, and western blotting were used to evaluate the effect of rehmapicrogenin on kidney injury in mice. In vitro , the effects of rehmapicrogenin on NRK-52E cellular damage induced by ADR were determined using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The mechanism was investigated using ELISA kits, flow cytometry and In-Cell Western™ blotting. In vivo , rehmapicrogenin treatment significantly attenuated the pathological changes in the kidney induced by ADR; rescued weight, serum creatinine (Scr), blood urea nitrogen (BUN) and urine albumin (U-ALB) levels; reduced reactive oxygen species (ROS) accumulation; and decreased oxidative stress, the apoptosis rate, and cell survival in ADR-treated mice. Importantly, both in vivo and in vitro experimental results demonstrated that rehmapicrogenin regulates the Nrf2/ARE signalling pathway, the most important pathway for oxidative stress. Rehmapicrogenin attenuated ADR-induced kidney damage by reducing oxidative stress through the oestrogen receptor pathway. Moreover, after treatment with ICI 182780 (the oestrogen receptor-nonspecific antagonist Faslodex), the improvement induced by rehmapicrogenin was significantly reversed. In conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway. [ABSTRACT FROM AUTHOR]

• 5-O-methyldihydroquercetin (GS1) and cilicicone B (GS2) were isolated from Spina Gleditsiae. • GS1 and GS2 have reno-protective effects via TLR4 signaling pathway. • GS1 and GS2 might be potential clinical drugs for AKI. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)-induced AKI. Spina Gleditsiae is a traditional Chinese anti-inflammatory medicine, from which a large number of flavonoids, such as 5-O-methyldihydroquercetin (GS1) and cilicicone B (GS2), were isolated in the present study. Here, we examined the reno-protective effects and potential underlying mechanisms of GS1 and GS2 in mice with LPS-induced AKI. We analyzed renal function; the serum metabolic profile, inflammatory cytokine levels, peripheral white blood cell count, renal cell apoptosis, renal oxidant and antioxidant levels, and renal expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), nuclear factor-ĸB (NF-ĸB), interferon regulatory factor 3 (IRF3), NOD-, LRR- and pyrin domain-containing 3 (NLRP3, inflammasome), cleaved caspase-1, and interleukin 1 receptor type I (IL-1R1) in mice with LPS-induced AKI. GS1 and GS2 improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. In addition, PCA score scatter plots suggest that the GS1 and GS2 groups were clustered with the control group, indicating that these compounds contributed to the recovery of mice with AKI toward the normal condition. Moreover, GS1 and GS2 inhibited the expression of TLR4, MyD88, TRIF, p-NF-ĸB, p-IRF3, NLRP3, cleaved caspase-1, and IL-1R1. The reno-protective effects of GS1 and GS2 are mediated via the MyD88/TRIF and NLRP3 pathways to reduce inflammation and oxidative stress through TLR4 signaling. [ABSTRACT FROM AUTHOR]