The Intervention and Mechanism of Action for Aloin against Subchronic Aflatoxin B1 Induced Hepatic Injury in Rats.

As a class of difurancoumarin compounds with similar structures, aflatoxins (AF) are commonly found in the environment, soil, and food crops. AF pose a serious threat to the health of humans, poultry, and livestock. This study aimed to investigate the neuroprotective effect and detailed mechanism of aloin on hepatic injury induced by subchronic AFB1 in rats. The result showed that aloin could significantly inhibit the decrease in food intake, body weight growth, immune organ index, and serum albumin content caused by long-term AFB1 exposure. Meanwhile, aloin reduced the level of serum liver function and improved renal swelling and pathological changes of liver tissue. Aloin could also inhibit liver lipid peroxidation and improve liver antioxidant capacity. Further investigation revealed that aloin inhibited the activity and expression of hepatic CYP1A2 and CYP3A4 and down-regulated IL-1ß expression in subchronic AFB1-induced liver injury rats. The above study demonstrated that aloin played an important role in blocking or delaying the development process of subchronic AFB1-induced hepatotoxicity. Therefore, aloin is considered to have a potential role as a protective agent against AFB1.

Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study.

Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia.

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.

The macamide relieves fatigue by acting as inhibitor of inflammatory response in exercising mice: From central to peripheral.

Macamides are the major and unique bioactive compounds of Lepidium meyenii (Walp.) or Maca. N-benzyl-(9Z, 12Z)-octadecadienamide (N-benzyl-linoleamide) is one of the most biologically active macamides with various pharmacological activities - anti-fatigue, neuroprotective, antioxidant, anti-tumoral activities, anti-inflammatory, and analgesic. In this study, the anti-fatigue properties of N-benzyl-(9Z, 12Z)-octadecadienamide were further evaluated by a weight-loaded forced swimming test. Results indicated N-benzyl-(9Z, 12Z)-octadecadienamide supplementation increased the forelimb grip strength of mice and exercising time remaining on the Rota-rod test. Furthermore, significant decreases in pro-inflammatory factors and reactive oxygen species (ROS) contents were observed in mice receiving N-benzyl-(9Z, 12Z)-octadecadienamide treatment after a 30 min swimming test, which was equivalent to that of caffeine. Histological analysis also indicated that N-benzyl-(9Z, 12Z)-octadecadienamide attenuated damage to the liver in mice by up-regulating the expression of heme oxygenase-1 (HO-1) and inhibiting the expression of Interleukin (IL)-1ß during exercise. Pearson correlation analysis suggested peripheral fatigue indexes, including energy sources, metabolites were significantly correlated with inflammatory factors and ROS levels. Likewise, central fatigue parameters are also associated, including hippocampal inflammatory response and hypothalamic neurotransmitters. Hence, macamides can be considered to have great potential as a natural drug with high efficiency and low side effects for fatigue management.

Comprehensive analysis of Sparassis crispa polysaccharide characteristics during the in vitro digestion and fermentation model.

Sparassis crispa (S.crispa), an edible mushroom, is widely used as a natural medicine due to its excellent pharmacological activities, including antitumor, anti-angiogenic, and immunomodulatory activities. In the current study, the digestion and fermentation characteristics of an S.crispa polysaccharide (SCP-1) were investigated by the in vitro simulated models. Our results revealed that SCP-1 was not degraded during the simulated gastrointestinal tract. However, it was consumed by human intestinal microbiota, which was characterized by enhancing the production of short-chain fatty acids (such as acetate, propionate, and butyrate), and modifying the gut microbiota composition through promoting beneficial genera (Prevotella 9, Dialister, Megamonas, and Megasphaera) and inhibiting proliferation of some harmful bacteria (i.e., Escherichia/Shigella). The PICRUSt prediction analysis indicated that SCP-1 significantly increased carbohydrate, energy, and amino acid metabolism. These results suggest that SCP-1 could be developed as a prebiotic addition and may improve host health by regulating gut microbiota.

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.

Effect of polysaccharides from Tibetan turnip (Brassica rapa L.) on the gut microbiome after in vitro fermentation and in vivo metabolism.

Tibetan turnip (Brassica rapa L.) polysaccharide (TTP) is an active ingredient and has been studied for many years due to its biological effect. There are a few studies on its digestion properties and the regulation of the intestinal microbiota. In this study, the regulation of intestinal health by TTP was investigated in vitro and in vivo. The results showed that TTP was not degraded after simulated gastrointestinal digestion. When TTP was fermented by the gut microbiota, the content of short-chain fatty acids (SCFAs) and the relative abundance of Bifidobacterium, Catenibacterium increased; the relative abundance of Prevotella, Phascolarctobacterium decreased. The in vivo experiments showed that TTP could reduce the abundances of Muribaculaceae and enrich Lactobacillus. The results of KEGG indicated that TTP could promote arginine and ornithine metabolism, fructose and mannose metabolism, and lipopolysaccharide biosynthesis. These data showed that TTP exerted its prebiotic effect by regulating the intestinal flora and could be used for preventing disease and improving health by maintaining intestinal health.

Aloe polysaccharides ameliorate acute colitis in mice via Nrf2/HO-1 signaling pathway and short-chain fatty acids metabolism.

Aloe polysaccharides (APs) are acetyl polysaccharides. It has been reported APs could protect mice from ulcerative colitis (UC), but the complex interactions between APs and the intestinal barrier were unclear. Here, we investigated the relationship between APs and UC, and determined the synergistic effects of Nrf2/HO-1 signaling pathway and short-chain fatty acids (SCFAs) metabolism on protecting intestinal barrier in acute UC mice. Results showed APs could scavenge free radicals in vitro. In vivo, APs had the antioxidant and anti-inflammatory effect both in serum and colon. Besides, the pathological results showed APs could alleviate colonic lesions. Furthermore, our study indicated treatment with APs effectively increased SCFAs production. The inhibition of acute UC in mice was correlated with the APs-mediated effects on improving the expression of ZO-1, occludin, Nrf2, HO-I, and NQO1. Thus, APs effectively promoted the intestinal barrier via Nrf2/HO-1 signaling pathway and SCFAs metabolism, effectively ameliorating acute colitis in mice.

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.

Macamides: A review of structures, isolation, therapeutics and prospects.

Macamides, the major bioactive compounds of Lepidium meyenii (Walp.) or Maca, are a unique class of non-polar, long chain fatty acid N-benzylamides with fertility-enhancing, neuroprotective, neuro-modulatory, anti-fatigue and anti-osteoporosis effects. However, the relationship between the structures and pharmacological effects of macamides have not been established so far. In addition, little is known regarding their biosynthetic pathways and the mechanisms underlying the biological activities. In this review, we have summarized the methods currently used for the extraction, purification and synthesis of macamides. Their pharmacological effects, clinical prospects and biomedical applications have also been discussed. Current data strongly suggest that macamides are a promising bio-active agent, and further studies are warranted to elucidate their mechanisms of action.

Torularhodin from Sporidiobolus pararoseus Attenuates d-galactose/AlCl3-Induced Cognitive Impairment, Oxidative Stress, and Neuroinflammation via the Nrf2/NF-κB Pathway.

Oxidative stress and neuroinflammation are considered as crucial culprits in Alzheimer's disease (AD). Torularhodin, a carotenoid pigment, possesses powerful antioxidant activity. This study aimed to elucidate the protective effects of torularhodin in the AD-like mouse model and investigated the underlying mechanisms. Behavioral and histopathological results suggested that torularhodin relieved cognitive impairments, attenuated Aß accumulation, and inhibited glial overactivation in d-gal/AlCl3-induced ICR mice. Simultaneously, torularhodin also markedly increased antioxidant enzyme capacities, lowered the contents of RAGE, and reduced levels of inflammatory cytokines. Western blot results showed that torularhodin ameliorated neuronal oxidative damage via activation of Nrf2 translocation, upregulation of HO-1, and inactivation of NF-κB in vivo and in vitro. Thus, torularhodin effectively ameliorated cognitive impairment, oxidative stress, and neuroinflammation, possibly through the Nrf2/NF-κB signaling pathways, suggesting torularhodin might offer a promising prevention strategy for neurodegenerative diseases.