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ObjectiveTo investigate the effects of Buyang Huanwutang （BYWHT） on reducing inflammatory injury and improving neurological function after cerebral ischemia-reperfusion in rats via activating the adiponectin （APN） pathway. MethodMale SD rats were randomized into sham， model， BYHWT （16 g·kg-1， twice a day）， and BYHWT + APN inhibitor （GW9662） groups. In the sham group， blood vessels were isolated. The rat model of middle cerebral artery occlusion （MCAO） was established. The rats in the BYHWT+GW9662 group was treated with subcutaneous injection of GW9662 at 4 m·kg-1 30 min before MCAO surgery and BYHWT at 16 g·kg-1 by gavage after MCAO surgery， once in the morning and once in the evening. The immunofluorescence （IF） assay was employed to observe the expression of adiponectin receptor 1 （AdipoR1） and the colocalization of AdipoR1 with neuronal nuclei （NeuN） and ionized calcium binding adaptor molecule 1 （Iba1） in the brain. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of APN in the serum and brain. The balance beam test was carried out to examine the balance ability， and the grasping test to assess the recovery of limb strength. The immunofluorescence assay was used to detect the expression of myeloperoxidase （MPO）. Western blot was employed to determine the expression of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， IL-6， and IL-10 and in the brain. ResultCompared with the sham group， the modeling promoted the expression of AdipoR1 （P<0.01）， lowered the APN levels in the serum and brain （P<0.05， P<0.01）， increased the score in the balance beam test （P<0.01）， and decreased the grasping strength of forepaw （P<0.01）， which were accompanied with increased MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and decreased IL-10 level （P<0.01）. Compared with the model group， BYHWT promoted the expression of AdipoR1 （P<0.01）， elevated APN levels in the serum and brain （P<0.05， P<0.01）， and increased the grasping strength of forepaw （P<0.01）， which were accompanied with lowered MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and elevated IL-10 level （P<0.01）. All the above effects were partially blocked by GW9662. ConclusionBYHWT can reduce inflammatory injury and improve neurological function in the rat model of cerebral ischemia-reperfusion by activating the APN pathway.
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OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adiponectin/metabolism , Antidepressive Agents/pharmacology , China , Depression/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Glucose , Hypothalamus/metabolism , Receptors, Adiponectin/metabolismABSTRACT
This study investigated the effects and mechanisms of 6-gingerol on adipose tissue insulin resistance in naturally aging rats with glycolipid metabolism disorders. Twenty-seven aging male SD rats were randomly divided into a model group(aged, n=9) and two groups treated with 6-gingerol at 0.05 mg·kg~(-1)(G-L, n=9) and 0.2 mg·kg~(-1)(G-H, n=9). Six young rats were randomly assigned to a normal control group(NC). Rats were treated for seven weeks by gavage. Non-esterified fatty acid(NEFA) and insulin content was determined by enzyme-linked immunosorbent assay(ELISA), and adipose tissue insulin resistance index(Adipo-IR) was calculated. HE staining was used to observe the size of adipocytes in epididymal white adipose tissue(eWAT). The gene and protein expression levels of adiponectin receptor 1(AdipoR1), AMP-activated protein kinase α(AMPKα), phosphorylated AMPK(p-AMPKα~(Thr172)), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), phosphorylated Akt(p-Akt~(Ser473)), tumor necrosis factor-α(TNF-α), c-Jun N-terminal kinase 1/2(JNK1/2), phosphorylated JNK1/2(p-JNK~(Thr183/Tyr185)), interleukin-1β(IL-1β), and interleukin-6(IL-6) in adiponectin(APN), insulin, and inflammatory factor signaling pathways were detected by Western blot and real-time RCR, respectively. The results showed that 6-gingerol at a high dose could significantly decrease the fasting plasma content of NEFA and insulin and reduce Adipo-IR. Additionally, 6-gingerol at a high dose significantly increased the protein and mRNA expression of APN, AdipoR1, PGC-1α, and PI3 K in eWAT, elevated the relative expression of p-AMPK~(Thr172) and p-Akt~(Ser 473), reduced the protein and mRNA expression of TNF-α, IL-1, and IL-6 in eWAT, and decreased the relative expression of p-JNK1 and p-JNK2. This study reveals that 6-gingerol can improve insulin sensitivity of adipose tissues in aging rats with glycolipid metabolism disorders, and this effect is presumedly achieved by enhancing the PI3 K/Akt signaling pathway, inhibiting adipose tissue inflammation, increasing APN synthesis, enhancing AdipoR1 expression, and activating its downstream AMPK/PGC-1α signaling pathway.
Subject(s)
Animals , Male , Rats , Adipose Tissue , Aging , Catechols , Fatty Alcohols , Insulin Resistance , Rats, Sprague-DawleyABSTRACT
AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .
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AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .