Chlorogenic acid improves the cognitive deficits of sleep-deprived mice via regulation of immunity function and intestinal flora.

BACKGROUND: Sleep deprivation (SD) has become a global health concern with serious consequences containing memory deficits and gastrointestinal dysfunctions. The gut-brain axis serves as a crucial link between the brain and gut, and the utilization of chlorogenic acid (CGA) presents a compelling strategy for mitigating or potentially resolving various neuroinflammation-associated disorders. However, it is still unknown how CGA may interact with the gut, microbiota and the brain during SD. PURPOSE: This study aims to explore the therapeutic effect and underlying mechanism of microbiota-gut-brain axis by which CGA prevents SD-induced cognitive deficits. STUDY DESIGN AND METHODS: CGA (30, 60 mg/kg.bw.) was gavaged to C57BL/6 mice, and then they were submitted to 48-h SD. The cognitive and spatial learning abilities were investigated through behavioral tests. Furthermore, we explored the action mechanism of this compound with haematological analysis, histopathological examination, Western blot, ELISA and 16S rRNA gene pyrosequencing from colonic contents. RESULTS: The cognitive deficits induced by SD were significantly relieved by administration of CGA in a dose-dependent manner. The hematoxylin and eosin staining of hippocampus and colon tissues indicated that pretreatment of CGA not only protected brain tissue from SD, but also maintained intestinal integrity. In the hippocampus, the increased pro-inflammatory neurometabolites were significantly prevented by CGA, and an immune profile capable of hippocampal-dependent spatial memory was improved via Nrf2/PPAR signaling pathways. The observed immunomodulatory effect was concomitant with augmentation of the intestinal barrier, as evidenced by the heightened expressions of tight junction proteins. 16S rRNA analysis of colonic contents revealed that levels of Clostridia_UCG-014 and lipopolysaccharide were significantly inhibited, and those of Lactobacillus and intestinal tight junction proteins were upregulated in the CGA group. Pathways of ko05322 (immune disease) and ko04610 (immune system) were significantly regulated by CGA. Based on PICRUSt2 algorithm, CGA probably influenced gut microbial functions via several metabolism pathways, such as arginine biosynthesis, pyrimidine metabolism and purine metabolism. CONCLUSION: The present study first proved the efficacy and mechanism of CGA in alleviating SD-induced cognitive impairment and neuroinflammation via creating a systemic protection, a bidirectional communication system connecting the gut with the brain. The intestinal barrier improvement and the reshaped "SD microbiota" profiles restored immunity functions, which were probably the main contributors to Nrf2/PPAR activation and the neuroprotective effect of CGA. Overall, this work provided novel insights of CGA, which might guide the more reasonable clinical use of CGA in the pathogenesis of sleep-related disorders.

Folic acid relieves bone cancer pain by downregulating P2X2/3 receptors in rats.

BACKGROUND: Bone cancer pain (BCP) remains a clinical challenge due to the limited and side effects of therapeutic methods. Folic acid has been known as an FDA approved dietary supplement and proved to have an analgesic effect in neuropathic pain. Here we investigate the role and mechanism of folic acid in bone cancer pain of a rat model. METHODS: Walker 256 tumor cells were inoculated into the left tibia of rats to induce bone cancer pain model. Pain reflex were assessed by paw withdrawal threshold (PWT) response to Von Frey filaments and paw withdrawal latency (PWL) response to thermal stimulation. Folic acid was injected intraperitoneally to evaluate its analgesic effect in rats with bone cancer pain. Western blotting and qPCR were used to determine P2X2/3 receptor protein and mRNA levels in ipsilateral L4-6 dorsal root ganglion (DRG) and spinal dorsal horn (SDH). RESULTS: The PWT and PWL of rats with bone cancer pain were obviously decreased compared to the naïve and sham rats. Interestingly, continuous folic acid treatment significantly increased the PWT and PWL of rats with bone cancer pain. P2X2 and P2X3 receptors were clearly upregulated at both mRNA and protein expression in L4-6 DRG and SDH of rats with bone cancer pain. P2X2 and P2X3 receptors were mainly localized with CGRP (calcitonin gene-related peptide) or IB4 (isolectin B4) positive neurons in L4-6 DRG of rats with bone cancer pain. Notably, continuous folic acid treatment significantly reduced the expression of P2X2 and P2X3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Finally, intrathecal injection of A317491 (a selective antagonist of P2X2/3 receptors) markedly elevated the PWT and PWL of rats with bone cancer pain. CONCLUSION: These results suggest that folic acid has an effective antinociceptive effect on bone cancer pain, which is mediated by downregulating P2X2/3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Folic acid may be a novel therapeutic strategy in cancer patients for pain relief.

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice.

SCOPE: Salidroside (SA) is an active compound derived from Rhodiola rosea and is widely used in healthcare foods. However, the underlying mechanism and its specific role in regulating the gut microbial community during exercise (Ex) remains unknown. METHODS AND RESULTS: Mice are subjected to a weight-loaded swimming test (WST) Ex to determine how gut microbiota affects the antifatigue activity of SA. The SA-treated group mice (100 mg kg-1 .bw.) display a significant increase in swimming time compared to the control group (26.2 versus 10.5 min, p < 0.01), as well as an increase in respiratory enzymatic activities after swimming. The respiratory enzymatic activities are significantly higher in the SA-treated group than in the RS (regular rest) group after swimming. The bacteria profiles in the Ex + SA group change significantly with higher species diversity and abundance. Receiver operating characteristic (ROC) curves of Alistipes, Rikenellaceae, Parabacteroides, Candidatus Arthromitus, and Lactobacillus indicate a high diagnostic utility to distinguish SA treatment. Microbial function analysis shows that SA may improve Ex-induced fatigue by modulating energy metabolism-related processes. CONCLUSIONS: SA demonstrates antifatigue effects on various levels of regulating energy metabolism and microbial composition, providing insights into the underlying mechanisms of SA as a natural prebiotic.

Traditional Chinese Medicine Syndrome of Primary Sjögren's Syndrome Patients with Interstitial Lung Disease / 中国实验方剂学杂志

ObjectiveTo summarize the characteristics of traditional Chinese medicine （TCM） syndrome in primary Sjögren's syndrome （pSS） patients with interstitial lung disease （ILD） and to explore associated factors. MethodA survey was conducted and pSS patients who were treated in TCM department of rheumatism at China-Japan Friendship Hospital from December 2018 to April 2022 were included. Tongue manifestations and syndromes of patients were recorded. pSS patients with ILD were classified into the pSS-ILD group and those without the ILD were included in the pSS-non-ILD group. The tongue manifestations， syndromes， and laboratory indexes were compared between the two groups， and logistic regression was used to explore the factors associated with pSS-ILD. ResultA total of 200 pSS patients were included， with 186 （93.0%） females， median age of 57 years， and median disease course of 60 months， of which 44 （22%） had pSS-ILD. In terms of tongue manifestations， pSS-ILD patients generally had dark/purple/stasis tongue， fissured tongue， and tongue with little fluid， thick coating， yellow coating， and greasy coating. The proportion patients with yellow coating was higher in pSS-ILD group than in the pSS-non-ILD group （χ2=4.799，P<0.05）. In terms of syndrome， more than 40% of pSS-ILD patients had Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. As for Yin deficiency， liver-kidney Yin deficiency syndrome ranked the first. For Qi deficiency， lung Qi deficiency syndrome was most commonly seen. The proportion of patients with lung Qi deficiency was higher in the pSS-ILD group than in the pSS-non-ILD group （χ2=18.667，P<0.01）. As to laboratory indexes， compared with the pSS-non-ILD group， pSS-ILD group had high proportion of anti-SSA-positive patients （P<0.05） and high levels of C-reactive protein （CRP） （P<0.01）， complement C3 （χ2=4.332，P<0.05）， and complement C4 （P<0.05）. Logistic regression analysis showed that pSS with ILD was positively associated with lung Qi deficiency ［odds ratio （OR）=6.079， 95% confidence interval （CI） 2.585-14.298， P<0.01）］ and yellow coating （OR=5.260， 95% CI 1.337-20.692， P<0.05） and negatively associated with low C4 （OR=0.199， 95% CI 0.070-0.564， P<0.01）. ConclusionAbout 22% of pSS patients had ILD， and patients with pSS-ILD generally have Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. Yellow coating， lung Qi deficiency and C4 level are factors associated with pSS combined with ILD.

Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis.

A growing number of nutraceuticals and cosmeceuticals have been utilized for millennia as anti-fatigue supplements in folk medicine. However, the anti-fatigue mechanism underlying is still far from being clearly explained. The aim of the study is to explore the underlying mechanism of the Maca compound preparation (MCP), a prescription for management of exercise-induced fatigue. In this study, mice weight-loaded swimming test was used to evaluate the anti-fatigue effect of MCP. MCP significantly improved the forelimb grip strength and Rota-rod test in behavioral tests via regulating energy metabolism. 16S rDNA sequencing results showed MCP can regulate the intestinal flora at the genus level by increasing several beneficial bacteria (i.e., Lactobacillus, Akkermansia and etc.), and decreasing the harmful bacteria (i.e., Candidatus_Planktophila and Candidatus_Arthromitus), where notable high relevance was observed between the fatigue-related biomarkers and fecal microbiota. The results of microbial function analysis suggested that MCP might improve exercise-induced fatigue by enhancing energy metabolism, carbohydrate and lipid metabolism and metabolism of terpenoids and polyketides and breakdown of amino acid metabolism. In addition, and H2O2-induced oxidative stress model on C2C12 cells was employed to further validate the regulation of MCP on energy metabolisms. MCP pre-treatment significantly reduced intracellular ROS accumulation, and increased glycogen content, ATP generation capacity and mitochondrial membrane potential of skeletal muscle cells, as well as conferred anti-cell necrosis ability. In conclusion, MCP plays a key role in regulating fatigue occurrence in exercising and gut microbiota balance, which may be of particular importance in the case of manual workers or sub-healthy populations.

An integrated network pharmacology and metabolomics approach to reveal the immunomodulatory mechanism of Brassica rapa L. (Tibetan Turnip) in fatigue mice.

Brassica rapa L. has been widely used as an edible, feeding and medicinal plant in the Qinghai-Tibet Plateau due to its several pharmacological effects of alleviating deficiency or weakness, anti-inflammation, and relieving acute mountain sickness. However, its therapeutic efficacy and the underlying mechanism against fatigue have not been elucidated. The aim of this study is to investigate the action mechanisms of Brassica rapa L. extract (BE) in treating fatigue, with emphasis on the fatigue-related biomarkers, targets and pathways, via network pharmacology and widely targeted metabolomics. Based on the UHPLC-MS results, a total of 33 components were identified and the energy metabolic homeostasis and inflammation related signaling pathways were considered crucial for BE against fatigue by gene functional enrichment analysis. Western blotting (WB) showed that BE significantly up-regulated Nrf2/HO-1, phosphorylation of AMPK, and expression of the downstream signaling pathway, which was further verified by quantitative real-time PCR (q Rt-PCR). The metabolic pathway analysis of BE showed that linoleic acid metabolism was mainly involved, as well as the generation and degradation of ketone bodies, and taurine and hypotaurine metabolism, which are closely related to the regulation of energy metabolism and immunoregulation. Furthermore, the drug-containing serum of BE attenuated intracellular ROS levels in macrophage Raw264.7 cells and reversed the M1 polarization by enhancing the level of IL-10 and Arg-1 and inhibiting that of IL-12 and iNOS in vitro. Hence, Brassica rapa L. has the potential to become a functional food or alternative therapy for fatigue management among immune-compromised people.

Brassica rapa L. (Tibetan turnip) prevents sleep-deprivation induced cognitive deficits via the inhibition of neuroinflammation and mitochondrial depolarization.

Brassica rapa L., an edible, feeding and medicinal plant cultivated on the Tibetan plateau with altitudes above 3800 m, has several pharmacological effects. However, its therapeutic effects against memory impairment and central fatigue have yet to be conclusively established. In this study, the Y-maze and Morris water maze tasks revealed that Brassica rapa L. aqueous extract (BE) significantly ameliorated cognitive deficits of sleep deprivation (SD)-treated mice. Moreover, BE treatment partially alleviated SD-induced reductions in the levels of peripheral energy metabolism, and significantly decreased inflammatory factor levels in serum and hippocampus. In addition, BE treatment significantly relieved central fatigue and stabilized the excitability as well as activities of neurons by regulating the levels of hypothalamus tryptophan metabolites and striatum neurotransmitters. The neuroprotective effects of BE were also confirmed using glutamate-treated HT22 cells, whereby BE pretreatment significantly attenuated intracellular ROS production and mitochondrial depolarization via adenosine 5'-monophosphate activated protein kinase/peroxisome proliferators-activated receptors (AMPK/PPAR-γ) signaling pathways. Thus, BE might probably prevent SD-induced learning and memory deficits by inhibiting neuroinflammation and restoring mitochondrial energy metabolism in the hippocampus. These findings imply that BE is a potential complementary therapy for those suffering from deficient sleep or neurometabolic disorders, although this needs verification by prospective clinical studies.

Network Pharmacology Exploration Reveals Gut Microbiota Modulation as a Common Therapeutic Mechanism for Anti-Fatigue Effect Treated with Maca Compounds Prescription.

Maca compounds prescription (MCP) is a common botanical used in dietary supplements, primarily to treat exercise-induced fatigue. The aim of this study is to elucidate the multi-target mechanism of MCP on fatigue management via network pharmacology and gut microbiota analysis. Databases and literature were used to screen the chemical compounds and targets of MCP. Subsequently, 120 active ingredients and 116 fatigue-related targets played a cooperative role in managing fatigue, where several intestine-specific targets indicated the anti-fatigue mechanism of MCP might be closely related to its prebiotics of intestinal bacteria. Thus, forced swimming tests (FSTs) were carried and mice fecal samples were collected and analyzed by 16S rRNA sequencing. Gut microbiota were beneficially regulated in the MCP-treated group in phylum, genus and OTU levels, respectively, and that with a critical correlation included Lactobacillus and Candidatus Planktophila. The results systematically reveal that MCP acts against fatigue on multi-targets with different ingredients and reshapes the gut microbial ecosystem.

Chicoric Acid Prevents Neuroinflammation and Neurodegeneration in a Mouse Parkinson's Disease Model: Immune Response and Transcriptome Profile of the Spleen and Colon.

Chicoric acid (CA), a polyphenolic acid compound extracted from chicory and echinacea, possesses antiviral, antioxidative and anti-inflammatory activities. Growing evidence supports the pivotal roles of brain-spleen and brain-gut axes in neurodegenerative diseases, including Parkinson's disease (PD), and the immune response of the spleen and colon is always the active participant in the pathogenesis and development of PD. In this study, we observe that CA prevented dopaminergic neuronal lesions, motor deficits and glial activation in PD mice, along with the increment in striatal brain-derived neurotrophic factor (BDNF), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HT). Furthermore, CA reversed the level of interleukin-17(IL-17), interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-ß) of PD mice, implicating its regulatory effect on the immunological response of spleen and colon. Transcriptome analysis revealed that 22 genes in the spleen (21 upregulated and 1 downregulated) and 306 genes (190 upregulated and 116 downregulated) in the colon were significantly differentially expressed in CA-pretreated mice. These genes were functionally annotated with GSEA, GO and KEGG pathway enrichment, providing the potential target genes and molecular biological mechanisms for the modulation of CA on the spleen and gut in PD. Remarkably, CA restored some gene expressions to normal level. Our results highlighted that the neuroprotection of CA might be associated with the manipulation of CA on brain-spleen and brain-gut axes in PD.

Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway.

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as a nutraceutical to combat inflammation, viruses and obesity. Parkinson's disease (PD) is a common neurodegenerative disorder, and the microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results obtained in this study demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunctions and death of nigrostriatal dopaminergic neurons along with the inhibition of glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of the gut microbiota to normal, including decreased phylum Bacteroidetes and genera Parabacteroide, as well as increased phylum Firmicutes, genera Lactobacillus and Ruminiclostridium. Besides, CA promoted colonic epithelial integrity and restored normal SCFA production. We also observed that proinflammatory cytokines such as TNF-α and IL-1ß in the serum, striatum and colon were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of the TLR4/MyD88/NF-κB signaling pathway might be the underlying molecular mechanism. These findings demonstrated that CA had neuroprotective effects on MPTP-induced PD mice possibly via modulating the gut microbiota and inhibiting inflammation throughout the brain-gut axis.

Material basis research for Echinacea purpurea (L.) Moench against hepatocellular carcinoma in a mouse model through integration of metabonomics and molecular docking.

BACKGROUND: Echinacea purpurea (L.) Moench (EP), a well-known "immunostimulant" in the West, is one of the most popular botanicals for patients with cancer. It has been proved to be effective against hepatocellular carcinoma (HCC), while the active ingredients remains unclear. PURPOSE: This study aimed to investigate the inhibitory effect and interpret the material basis of EP against HCC through metabolomics and molecular docking. METHODS: Tumor growth, biochemical analysis and pathological changes were detected in HCC-induced mice to evaluate the efficacy of EP. An integrative method combining molecular docking and LC-MS-based metabolomics was performed to evaluate the inhibitory role and screen the material basis of EP against HCC. RESULTS: EP significantly suppressed tumor growth and decreased the levels of AFP. Histological analysis showed that wide areas of necrosis in the EP-treated tumors that were almost absent in those in model group. Serum metabolomics results revealed EP could significantly improve 12 serum different metabolites induced by HCC, which were involved into phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Then, 5 related genes were selected out to be the key targets of EP against HCC based on Metscape. 22 identified compounds were docked through Sybyl-X. The herb-compound-gene-metabolic pathways network (HCGMN) was constructed to reveal the associations between EP and HCC. Finally, 19 compounds were screened as promising active ingredients of EP against HCC. CONCLUSION: The results showed that the approach integrating of metabonomics and molecular docking is a powerful strategy to obtain the active ingredients from plants.

Echinacea purpurea suppresses the cell survival and metastasis of hepatocellular carcinoma through regulating the PI3K/Akt pathway.

Echinacea purpurea (L.) Moench (Ep) is widely used as a kind of dietary supplements, and possesses various pharmacological activities, including immunomodulatory, anti-inflammatory, antitumor effects. However, the inhibitory effects of Ep on the growth and metastasis of hepatocellular carcinoma (HCC) is unclear. Here, the preventive effect and potential mechanism of Ep on HCC was elucidated by systems pharmacology and molecular docking. The results showed that Ep could significantly ameliorate HCC-induced tumor growth and migration in vivo and in vitro. System pharmacology results indicated that 180 genes associated with HCC were regarded as the potential therapeutic targets of Ep, mainly involved in metabolic pathways, cancer pathways, proteoglycans in cancer and PI3K/Akt signaling pathway, which might be a crucial pathway in HCC EMT. A herb-component-target-pathway network was constructed to reveal the interactions between Ep and HCC. Finally, predicted PI3K/Akt pathway was further validated by molecular docking and western blot experiment. This study showed that Ep ameliorates HCC-induced tumor cell survival and migration in mice via the regulation of the PI3K/Akt pathway. Thus, Ep might be a potential new strategy to prevent the growth and metastasis of HCC.

Synergistic interactions of plant essential oils with antimicrobial agents: a new antimicrobial therapy.

The problem of drug resistance of food borne pathogens is becoming more and more serious. Although traditional antimicrobial agents have good therapeutic effects on a variety of food borne pathogens, more effective antimicrobial agents are still needed to combat the development of drug-resistant food borne pathogens. Plant-based natural essential oils (EOs) are widely used because of their remarkable antimicrobial activity. A potential strategy to address food borne pathogens drug resistance is to use a combination of EOs and antimicrobial agents. Because EOs have multi-target inhibitory effects on microorganisms, combining them with drugs can enhance the activity of the drugs and avoid the emergence of food borne pathogens drug resistance. This paper introduces the main factors affecting the antibacterial activity of EOs and describes methods for evaluating their synergistic antibacterial effects. The possible mechanisms of action of EOs and the synergistic inhibitory effects on pathogens of EOs in combination with antimicrobial agents is described. In summary, the combined use of EOs and existing antimicrobial agents is a promising potential new antibacterial therapy.

Research progress of the classic prescription Tianwang buxin dan in the treatment of insomnia / 中国药房

Tianwang buxin dan （TWBXD），as a classic prescription for treating insomnia ，in forms of tablet ，drop pill ，patch and others ，has been widely used in clinical practice . Its compound prescription and single ingredient can play a calming and tranquilizing role by regulating neurotransmitters ，inhibiting oxidative stress reaction and the expression of inflammatory factors . Based on the theory of traditional Chinese medicine and combined with modern pharmacological research ，this paper reviews single ingredient and active components of TWBXD ，calming and tranquilizing role of related couplet medicinals . The results showed that the single ingredients such as Rehmannia glutinosa ，the seeds of Zizyphus jujube ，the seeds of Platycladus orientalis ，Angelica sinensis，Schisandra chinensis ，Poria cocos and their effective components as well as related couplet medicinals of Z. jujube could improve the insomnia symptoms in different degrees . Except that the mechanism of the seeds of P. orientalis has not been studied ， other ingredients mainly act on nervous -endocrine-immune system . They can play the sedative and hypnotic effects by regulating neurotransmitters，inflammatory factors and oxidation .

Magnesium-L-threonate alleviate colonic inflammation and memory impairment in chronic-plus-binge alcohol feeding mice.

Magnesium-l-threonate (MgT) is considered a food supplement. Alcohol-mediated diseases (AMD) are accompanied by inflammation and memory impairment. The purpose of this study is to investigate the function of MgT in AMD. Hence, chronic-plus-binge alcohol feeding mice model and multiply bioinformatics analysis were performed. Consequently, the expression of inflammatory cytokines downregulated, while the activities of antioxidases decreased in serum, colon, and brain. Interestingly, MgT relieved gut barrier dysfunction and reshaped microbiota. The relative abundance of Akkermansia, Odoribacter, and Blautia were increased, while that of Alloprevotella and Clostridium were decreased. Metabolic analysis elucidated amino acids and glutamate metabolism were enhanced in MgT-treated mice. Furthermore, morris water maze test confirmed memory ability was enhanced. Inflammation cytokines were negatively correlated with Blautia, and Akkermansia. Collectively, MgT relieved inflammation in gut-brain axis of mice, reshaped gut microbiota, and enhanced the amino acids and glutamate metabolism. MgT may be used as a food supplement to prevent inflammation and memory impairment induced by alcohol abuse.

Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety.

BACKGROUND: Echinacea, one of the most popular herbs with double function of immunity and anti-inflammatory activity, has now attracted much interest for a possible alternative for the treatment of hepatopathy. This review is aimed at providing a comprehensive overview of Echinacea regarding its chemical composition, pharmacological action against various hepatopathy, and safety. METHODS: A comprehensive search of published articles was conducted to focus on original publications related to Echinacea and hepatopathy till the end of 2020 using various literature databases, including China National Knowledge Infrastructure, PubMed, and Web of Science database. RESULTS: Echinacea exhibited excellent activities in resisting a variety of hepatopathy induced by different causes in preclinical experiments and clinical trials by regulating cell proliferation and apoptosis, antioxidant defense mechanism, voltage-gated sodium channels, lipid metabolism, circadian rhythm, p38 MAPK signaling pathway, JNK signaling pathway, Nrf2/HO-1 signaling pathway, PI3K/AKT signaling pathway, and Akt/GSK3 beta signaling pathways. The high efficacy of Echinacea is related to its immunomodulatory and anti-inflammatory activities. The main ingredients of Echinacea include caffeic acid derivatives, alkylamides, and polysaccharides, which have been well established in preclinical studies of liver diseases. Studies on acute and subacute toxicity show that Echinacea preparations are well-tolerated herbal medicines. CONCLUSION: Echinacea may offer a novel potential strategy for clinical prevention and treatment of liver diseases and related diseases. Extensive studies are necessary to identify the underlying mechanisms and establish future therapeutic potentials of this herb. Well-designed clinical trials are still warranted to confirm the safety and effectiveness of Echinacea for hepatopathy.

Anti-fatigue effect of Lepidium meyenii Walp. (Maca) on preventing mitochondria-mediated muscle damage and oxidative stress in vivo and vitro.

Maca (Lepidium meyenii Walp.) has emerged as a popular functional plant food due to its various pharmacological properties, including anti-oxidation, anti-inflammation and anti-fatigue activity. In this study, we investigated the role of Maca aqueous extract (ME) on muscle during exercise-induced fatigue both in vivo and in vitro. As a result, ME significantly enhanced mouse leg grip-strength and increased exercise endurance in the rota-rod test. ME could clear the accumulation of metabolites - blood lactic acid (BLA), blood urea nitrogen (BUN) and reactive oxygen species (ROS) levels after weight-loaded forced swimming. Focusing on muscle, we found that the administration of ME strengthened mouse muscle structures so that exercise-induced metabolic stress was alleviated by upregulating NAD+/NADH. Furthermore, ME inhibited the reduction of the viability and accumulation of ROS by treatment with H2O2 in C2C12 skeletal muscle cells. ME-induced activation of energy metabolism in skeletal muscle might up-regulate mitochondrial biogenesis and function, thereby protecting against oxidative stress-induced damage. We concluded that the effects of Maca played a crucial role in the regulation of exercise-induced fatigue in mouse muscle, which could be expected to serve as a functional food supplement for improving exercise performance and alleviating physical fatigue.

Bioactive compound from the Tibetan turnip (Brassica rapa L.) elicited anti-hypoxia effects in OGD/R-injured HT22 cells by activating the PI3K/AKT pathway.

Cerebral stroke, a common clinical problem, is the predominant cause of disability and death worldwide. Its prevalence increases and infarctions exacerbate with age. A Tibetan plant, Brassica rapa L., possesses multiple medicinal effects, such as anti-altitude sickness, anti-hyperlipidemia and anti-fatigue, as mentioned in the noted ancient Tibet pharmacopeia "The Four Medical Tantras". Our preliminary studies also showed the anti-hypoxia protection mechanism of B. rapa L., implying its possible relationship with anti-ischemic neuroprotection. However, the potential molecular mechanism of the active constituent of turnip against cerebral ischemia/reperfusion remains unclear. In our study, oxidative stress markers, including LDH, ROS, SOD, GPx and CAT were assayed. In controlled in vitro assays, we found that the turnip's active constituent had remarkable anti-hypoxia capability. We further showed the profound effects of the active constituent of turnip on the levels of apoptosis-related proteins, including Bax, Bcl-2 and caspase-3, which contributed to its anti-inflammatory activity. Western blot analysis results also implied that active-constituent pretreatment reversed the diminished expression of the PI3K/Akt/mTOR pathway mediated by oxygen glucose deprivation/reperfusion (OGD/R); further experimental evidence showed that the protective role was limited in the PI3K inhibitor (LY294002) treatment group. Our results demonstrated that the functional monomer of B. rapa L. exerted a neuroprotective effect against OGD/R-induced HT22 cell injury, and its potential mechanism provides a scientific basis for future clinical applications and its use as a functional food.

Neuroprotection against cerebral ischemia/reperfusion by dietary phytochemical extracts from Tibetan turnip (Brassica rapa L.).

ETHNOPHARMACOLOGICAL RELEVANCE: The Tibetan turnip (Brassica rapa L.) has a wide array of medicine properties including heat-clearing, detoxifying and anti-hypoxia as listed in the famous centuries-old Tibetan medicine classic "The Four Medical Tantras". Evidence-based medicine also indicated the anti-hypoxic effect of turnips, suggesting a potential link to neuroprotective effect on ischemic stroke. This thereby enables turnips to serve as a novel nontoxic agent in related treatment. AIM OF THE STUDY: This study aimed to investigate the neuroprotective effect and elucidate the mechanism of aqueous extract of turnip (AET) on cerebral ischemia/reperfusion. MATERIALS AND METHODS: The experimental models of cerebral ischemia included transient middle cerebral artery occlusion/reperfusion (MCAO) in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in HT-22 cells. Long-term effect of AET on infarct volume was evaluated by microtubule-associated protein 2 (MAP2) immunofluorescence 28 days after MCAO, and on neurofunctional outcomes determined by rotarod, grid walking, and cylinder tests in the meantime. Efficacy of AET was determined by the cell viability, the release of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in neurons. The underlying mechanism of AET rescued OGD/R cells were characterized by PI3K, Akt and mTOR expressions, which were further used to validate AET's role in the pathway. RESULTS: AET can reduce cerebral infarct volume and ameliorate behavioral deficits of MCAO/R mice dose-dependently. In vitro experiment further demonstrated that suitable concentrations of AET inhibited ROS, LDH production and restored mitochondrial expression induced by OGD/R. AET pretreatment can reverse the OGD/R-induced decreased level of phosphorylation of PI3K, Akt, mTOR, whereas this effect was blocked in the LY294002 (PI3K inhibitor) treatment group. CONCLUSIONS: AET improved the survival of OGD/R-injured HT-22 cells by activating the PI3K/Akt/mTOR pathway. Based on the results above, aqueous extract of turnip has a protective effect on focal cerebral ischemic injury.

Isolation of two sesquiterpene glycosides from Sapindus mukorossi Gaertn. with cytotoxic properties and analysis of their mechanism based on network pharmacology.

The anti-tumor effects of two compounds purified from Sapindus mukorossi Gaertn. (S. mukorossi.) on breast cancer in vitro were observed. Their chemical structures were identified as sesquiterpene glycosides, namely, Mukurozioside IIa and Mukurozioside IIb. The results of XTT assay indicated that their inhibition rates against three cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-435s) reached approximately 80% at a concentration of 200 µg/mL, which were higher than that of cyclophosphamide (below 40% at 200 µg/mL), and their 50% inhibiting concentrations were ranged from 120.73 to 154.01 µg/mL, indicating their inhibition were weaker than their parent fraction. Furthermore, the mechanism on breast cancer was predicted, and 22 targets including PTPN1, IL2 and VEGFA were relatively important. These results illustrated the anti-breast cancer activity of S. mukorossi was related to the two compounds with the structure of sesquiterpene glycosides, but they did not represent the full activity of their parent fraction.