Anwulignan alleviates d-galactose induced renal damage by regulating Nrf2/ARE signaling pathway in mice.

Free radical accumulation in the body will cause oxidative stress damages including the renal damage. Schisandrae Sphenantherae Fructus (Schisandra), a traditional Chinese herbal medicine, has been used throughout the world. Anwulignan, a monomer extracted from Schisandra, has been shown in our previous studies to possess antioxidant and protective effects on the liver, brain and spleen damages in the aging mice. However, its effect on the renal damage caused by aging is not clear. This study showed that anwulignan could significantly increase the kidney index, the creatinine clearance, the activities of superoxide dismutase, catalase and glutathione peroxidase; reduce the urinary protein concentration, the serum urea nitrogen and creatinine content, the content of malondialdehyde and 8-hydroxylated deoxyguanosine in the renal tissue; and improve the renal tissue damage. Moreover, anwulignan increased the production of Nrf2, HO-1 and NQO1 proteins and decreased the production level of Keap1 protein in the renal tissue in the d-galactose induced aging mice. These results suggest that anwulignan significantly alleviates the renal damage by its antioxidant effect through regulating the production of Nrf2/ARE pathway-related proteins in the renal tissue in the d-galactose induced aging mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00951-7.

Protective Effects of Anwulignan against HCl/Ethanol-Induced Acute Gastric Ulcer in Mice.

Gastric ulcer is one of the most common gastrointestinal diseases. Anwulignan (AN) is a major active component of Schisandra sphenanthera Rehd. This study was designed to evaluate the protective effect of AN against the acute gastric ulcer induced by HCl/ethanol in mice. The mice were given HCl/ethanol by gavage to establish an acute gastric ulcer model. Then, the serum and gastric tissue samples were taken for biochemical analyses. The results showed that the pretreatment with AN could significantly reduce the gastric ulcer index (GUI) and increase the ulcer inhibition rate, indicating that AN can protect against gastric ulcers. AN showed its antioxidant roles by decreasing the content of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and anti-inflammatory roles by decreasing the content of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and myeloperoxidase (MPO) and increasing the content of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), prostaglandin E2 (PGE2), and nitric oxide (NO) in both serum and gastric tissue. Furthermore, AN also activated the NRF2/ARE signaling pathway and inhibited the MAPK/NF-κB signaling pathway. AN improves the acute gastric ulcer induced by HCl/ethanol in mice, which may be mainly through its antioxidant capacity and anti-inflammatory effect.

Anwulignan Ameliorates the Intestinal Ischemia/Reperfusion.

Anwulignan is one of the monomer compounds in the lignans from Schisandra sphenanthera In this study, we observed the effect of anwulignan on intestinal ischemia/reperfusion (II/R) injury in male Sprague-Dawley rats and explored the underlying mechanisms. The results showed that pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathologic injury of jejunum; enhance the autonomic tension of jejunum smooth muscle and its reactivity to acetylcholine; increase the activities of superoxide dismutase, catalase, glutathione S-transferase, and choline acetyltransferase; increase the contents of acetylcholine and glutathione in the serum or jejunal tissue; decrease the activities of myeloperoxidase, protein kinase C, and nicotinamide adenine dinucleotide phosphate oxidase; reduce the contents of malondialdehyde, 8-hydroxy-2-deoxyguanosine, nicotinamide adenine, reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß; increase the expression levels of muscarinic receptor 3, PI3K, phosphorylation protein kinase B, p-GSK3ß Ser9, Nrf2, p-Nrf2, heme oxygenase (decycling) 1, and b-cell lymphoma 2 in the jejunal tissue; and decrease the expression levels of p-GSK3ß Tyr216, kelch-like ECH-associated protein 1, Bax, and cleaved caspase-3, suggesting that anwulignan can ameliorate II/R-induced jejunal tissue injury in rats and that the mechanism may be related to its activating the PI3K/protein kinase B pathway and then regulating the Nrf2/Anti-oxidative Response Element signaling pathway and the expression of apoptosis-related proteins to play antioxidant and antiapoptotic roles. SIGNIFICANCE STATEMENT: Anwulignan can significantly reduce jejunal tissue injury and the production of inflammatory factors in rats with intestinal ischemia-reperfusion injury, improve the antioxidant capacity, and reduce the apoptosis of jejunal tissue, and it has the effect of significantly improving intestinal ischemia-reperfusion injury in rats, suggesting that anwulignan may be used as a potential drug for the prevention and treatment of intestinal ischemia-reperfusion injury or a resource for the development of health food.

Schisantherin A improves learning and memory abilities partly through regulating the Nrf2/Keap1/ARE signaling pathway in chronic fatigue mice.

Chronic fatigue is frequently accompanied by decreased learning and memory capabilities. Schizantherin A (SCA) is one of the main active monomer components in Schisandra chinensis lignans. In the present study, a chronic fatigue mouse model was established using the exhausted swimming approach to investigate the effects of SCA on learning and memory and its associated mechanism of action. Learning and memory abilities were tested by step through tests and water maze methods. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in hippocampal tissue were measured by corresponding assays. The effect of SCA on the expression of kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, Bax and cleaved caspase-3 were determined by western blot. The present results showed that SCA can improve the learning and memory capabilities of chronic fatigue mice. SCA was found to increase the activities of SOD and CAT in addition to increasing the levels of GSH but reduced the levels of MDA in hippocampus tissues. Furthermore, SCA treatment downregulated the protein expression levels of Keap1, Bax and cleaved caspase-3 and upregulated the protein expression levels of Nrf2, HO1 and Bcl2 in the hippocampus. These results suggested that modulations in the Nrf2-Keap1-antioxidant response element pathway, anti-oxidative and anti-apoptosis effects are the causes underlying the improvements from SCA treatment on the learning and memory abilities of chronic fatigue mice.

Anti-fatigue effect of anwulignan via the NRF2 and PGC-1α signaling pathway in mice.

OBJECTIVE: To examine the anti-fatigue function of anwulignan from Schisandra and its underlying mechanism. METHODS: After an excessive fatigue mouse model was created, anwulignan was administered to the mice, and its effect on exercise tolerance was studied by the weight-bearing swimming test, rotarod test, grip strength test, and tail suspension test. The biochemical indicators closely related to fatigue, including blood urea nitrogen (BUN), lactic acid (LD), lactate dehydrogenase (LDH), and creatine kinase (CK) in the serum; liver glycogen (LG) in the liver tissue; muscle glycogen (MG); inorganic phosphate (Pi) and Annexin V in the gastrocnemius; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA), catalase (CAT), and thiobarbituric acid reactive substances (TBARS); and the 8-hydroxy-2-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) content in both serum and the gastrocnemius were detected. Morphological changes were also observed. The anti-fatigue-related proteins of the NRF2/ARE, Bcl2, and PGC-1α pathways in the gastrocnemius of the mice were detected by western blot. RESULTS: Anwulignan significantly increased the exercise tolerance by decreasing BUN, LD, LDH, CK, Pi, MDA, TBARS, 8-OHdG, ROS, and Annexin V levels and increasing LG, MG, SOD, CAT, and GSH-Px levels, significantly upregulated the expression of NRF2 and Bcl2 proteins, which are anti-oxidation and anti-apoptosis regulators, and also activated the p38MAPK-PGC-1α pathway. CONCLUSION: Anwulignan can increase exercise tolerance and relieve fatigue in an excessive fatigue mouse model. The underlying mechanism may be through its regulatory effect on the NRF2 and PGC-1α signaling pathway. This study will provide scientific data for anwulignan to be developed as a novel and efficient component in anti-oxidant or anti-fatigue health food.

Molecular identification of Neofabraea species associated with bull's-eye rot on apple using rolling-circle amplification of partial EF-1α sequence.

A rolling-circle amplification (RCA) method with padlock probes targeted on EF-1α regions was developed for rapid detection of apple bull's-eye rot pathogens, including Neofabraea malicorticis, N. perennans, N. kienholzii, and N. vagabunda (synonym: N. alba). Four padlock probes (PLP-Nm, PLP-Np, PLP-Nk, and PLP-Nv) were designed and tested against 28 samples, including 22 BER pathogen cultures, 4 closely related species, and 2 unrelated species that may cause serious apple decays. The assay successfully identified all the bull's-eye rot pathogenic fungi at the level of species, while no cross-reaction was observed in all target species and no false-positive reaction was observed with all strains used for reference. This study showed that the use of padlock probes and the combination of probe signal amplification by RCA provided an effective and sensitive method for the rapid identification of Neofabraea spp. The method could therefore be a useful tool for monitoring bull's-eye rot pathogens in port quarantine and orchard epidemiological studies.