ShuYu capsule alleviates emotional and physical symptoms of premenstrual dysphoric disorder: Impact on ALLO decline and GABAA receptor δ subunit in the PAG area.

Premenstrual dysphoric disorder (PMDD) is a severe subtype of premenstrual syndrome in women of reproductive age, with its pathogenesis linked to the heightened sensitivity of type A γ -aminobutyric acid receptors (GABAAR) to neuroactive steroid hormone changes, particularly allopregnanolone (ALLO). While a low dose of fluoxetine, a classic selective serotonin reuptake inhibitor, is commonly used as a first-line drug to alleviate emotional disorders in PMDD in clinical settings, its mechanism of action is related to ALLO-GABAA receptor function. However, treating PMDD requires attention to both emotional and physical symptoms, such as pain sensitivity. This study aims to investigate the efficacy of ShuYu capsules, a traditional Chinese medicine, in simultaneously treating emotional and physical symptoms in a rat model of PMDD. Specifically, our focus centres on the midbrain periaqueductal grey (PAG), a region associated with emotion regulation and susceptibility to hyperalgesia. Considering the underlying mechanisms of ALLO-GABAA receptor function in the PAG region, we conducted a series of experiments to evaluate and define the effects of ShuYu capsules and uncover the relationship between the drug's efficacy and ALLO concentration fluctuations on GABAA receptor function in the PAG region. Our findings demonstrate that ShuYu capsules significantly improved oestrous cycle-dependant depression-like behaviour and reduced stress-induced hyperalgesia in rats with PMDD. Similar to the low dose of fluoxetine, ShuYu capsules targeted and mitigated the sharp decline in ALLO, rescued the upregulation of GABAAR subunit function, and activated PAG neurons in PMDD rats. The observed effects of ShuYu capsules suggest a central mechanism underlying PMDD symptoms, involving ALLO_GABAA receptor function in the PAG region. This study highlights the potential of traditional Chinese medicine in addressing both emotional and physical symptoms associated with PMDD, shedding light on novel therapeutic approaches for this condition.

Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials.

Objectives: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC. Methods: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0. Results: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate. Conclusions: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

Looking for a Beam of Light to Heal Chronic Pain.

Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.

CRTC2 activates the epithelial-mesenchymal transition of diabetic kidney disease through the CREB-Smad2/3 pathway.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a key role in tubulointerstitial fibrosis, which is a hallmark of diabetic kidney disease (DKD). Our previous studies showed that CRTC2 can simultaneously regulate glucose metabolism and lipid metabolism. However, it is still unclear whether CRTC2 participates in the EMT process in DKD. METHODS: We used protein‒protein network (PPI) analysis to identify genes that were differentially expressed during DKD and EMT. Then, we constructed a diabetic mouse model by administering STZ plus a high-fat diet, and we used HK-2 cells that were verified to confirm the bioinformatics research results. The effects that were exerted by CRTC2 on epithelial-mesenchymal transition in diabetic kidney disease through the CREB-Smad2/3 signaling pathway were investigated in vivo and in vitro by real-time PCR, WB, IHC and double luciferase reporter gene experiments. RESULTS: First, bioinformatics research showed that CRTC2 may promote EMT in diabetic renal tubules through the CREB-Smad2/3 signaling pathway. Furthermore, the Western blotting and real-time PCR results showed that CRTC2 overexpression reduced the expression of E-cadherin in HK-2 cells. The CRTC2 and α-SMA levels were increased in STZ-treated mouse kidneys, and the E-cadherin level was reduced. The luciferase activity of α-SMA, which is the key protein in EMT, was sharply increased in response to the overexpression of CRTC2 and decreased after the silencing of CREB and Smad2/3. However, the expression of E-cadherin showed the opposite trends. In the real-time PCR experiment, the mRNA expression of α-SMA increased significantly when CRTC2 was overexpressed but partially decreased when CREB and Smad2/3 were silenced. However, E-cadherin expression showed the opposite result. CONCLUSION: This study demonstrated that CRTC2 activates the EMT process via the CREB-Smad2/3 signaling pathway in diabetic renal tubules.

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD). Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining. Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms. Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.

Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD.

Curcumin (CUMINUP60®) mitigates exercise fatigue through regulating PI3K/Akt/AMPK/mTOR pathway in mice.

Curcumin is a chemical constituent extracted from Curcuma longa L. Several clinical and preclinical studies have demonstrated that it can mitigate exercise fatigue, but the exact mechanism is still unknown. Therefore, we applied a mouse model of exercise fatigue to investigate the possible molecular mechanisms of curcumin's anti-fatigue effect. Depending on body mass, Kunming mice were randomly divided into control, caffeine (positive drug), and curcumin groups, and were given 28 days intragastric administration. Both the caffeine group and curcumin group showed significant improvement in exercise fatigue compared to the control group, as evidenced by the increase in time to exhaustion, as well as the higher quadriceps coefficient, muscle glycogen (MG) content, and increase in the expression of Akt, AMPK, PI3K, and mTOR proteins. While the curcumin group also significantly improved the exercise fatigue of the mice, demonstrating a lower AMP/ATP ratio and lactic acid (LA) content, and increased glycogen synthase (GS), and myonectin content compared to the caffeine group. Therefore, in the present study, we found that curcumin can exert a similar anti-fatigue effect to caffeine and may act by regulating energy metabolism through modulating the expression of the proteins in the PI3K/Akt/AMPK/mTOR pathway.

Glyphosate-induced autophagy inhibition results in hepatic steatosis via mediating epigenetic reprogramming of PPARα in roosters.

Glyphosate (Gly) is the most widely used herbicide with well-defined hepatotoxic effects, but the underlying mechanisms of Gly-induced hepatic steatosis remain largely unknown. In this study, a rooster model combined with primary chicken embryo hepatocytes was established to dissect the progresses and mechanisms of Gly-induced hepatic steatosis. Data showed that Gly exposure caused liver injury with disrupted lipid metabolism in roosters, manifested by significant serum lipid profile disorder and hepatic lipid accumulation. Transcriptomic analysis revealed that PPARα and autophagy-related pathways played important roles in Gly-induced hepatic lipid metabolism disorders. Further experimental results suggested that autophagy inhibition was involved in Gly-induced hepatic lipid accumulation, which was confirmed by the effect of classic autophagy inducer rapamycin (Rapa). Moreover, data substantiated that Gly-mediated autophagy inhibition caused nuclear increase of HDAC3, which altered epigenetic modification of PPARα, leading to fatty acid oxidation (FAO) inhibition and subsequently lipid accumulation in the hepatocytes. In summary, this study provides novel evidence that Gly-induced autophagy inhibition evokes the inactivation of PPARα-mediated FAO and concomitant hepatic steatosis in roosters by mediating epigenetic reprogramming of PPARα.

Inhibited transcription factor EB function induces reactive oxygen species overproduction to promote pyroptosis in cadmium-exposed renal tubular epithelial cells.

Pyroptosis is a pro-inflammatory type of cell death involved in the pathogenesis of multiple kidney diseases, while transcription factor EB (TFEB) is shown to be important for rescuing renal function. Cadmium (Cd) is an omnipresent toxic heavy metal with definite nephrotoxicity, but there is lacking of evidence regarding an interplay between TFEB activity and pyroptosis during Cd exposure. In this study, Cd-exposed NRK-52E cells were used to clarify this issue as an in vitro model of acute kidney injury. First, our results showed that Cd exposure evidently elevated the protein levels involved in pyroptosis, increased lactate dehydrogenase (LDH) release, and disrupted the cell membrane integrity, suggesting the occurrence of pyroptosis in NRK-52E cells. It is also shown that Cd induced a burst of reactive oxygen species (ROS) to mediate pyroptosis. Simultaneously, downregulated TFEB expression with its inhibited nuclear translocation was revealed in Cd-exposed NRK-52E cells. Further investigations have demonstrated that TFEB knockdown promoted Cd-induced ROS production to exacerbate the pyroptosis, while TFEB overexpression inhibited Cd-induced ROS production to alleviate the pyroptosis in NRK-52E cells. In summary, these findings demonstrate that Cd-inhibited TFEB function results in ROS overproduction to promote pyroptosis in NRK-52E cells, which provide new insight into the therapeutic targets for Cd-induced kidney diseases.

Oxytocin and serotonin in the modulation of neural function: Neurobiological underpinnings of autism-related behavior.

Autism spectrum disorders (ASD) is a group of generalized neurodevelopmental disorders. Its main clinical features are social communication disorder and repetitive stereotyped behavioral interest. The abnormal structure and function of brain network is the basis of social dysfunction and stereotyped performance in patients with autism spectrum disorder. The number of patients diagnosed with ASD has increased year by year, but there is a lack of effective intervention and treatment. Oxytocin has been revealed to effectively improve social cognitive function and significantly improve the social information processing ability, empathy ability and social communication ability of ASD patients. The change of serotonin level also been reported affecting the development of brain and causes ASD-like behavioral abnormalities, such as anxiety, depression like behavior, stereotyped behavior. Present review will focus on the research progress of serotonin and oxytocin in the pathogenesis, brain circuit changes and treatment of autism. Revealing the regulatory effect and neural mechanism of serotonin and oxytocin on patients with ASD is not only conducive to a deeper comprehension of the pathogenesis of ASD, but also has vital clinical significance.

A novel curcumin oil solution can better alleviate the motor activity defects and neuropathological damage of a Parkinson's disease mouse model.

Curcumin has been reported to improve or prevent movement disorders in Parkinson's disease (PD); however, its low bioavailability is the biggest obstacle to its application. To optimize the limited efficacy of curcumin and to improve its protective effects against PD, we prepared and tested a novel curcumin oil solution. In vivo imaging was used to confirm that the curcumin oil solution has higher bioavailability than curcumin alone. To test its motor effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced movement disorders, behavioral tests, including the open-field test, pole test, rotarod test, and automated gait analysis were used. Finally, pathological evaluation using immunohistochemistry and western blotting analysis was done. Encouragingly, the behavioral test findings exhibited a better protective effect against MPTP-induced movement disorders. In addition, it had a greater protective effect on dopaminergic neurons in the compact part of the substantia nigra along with the PD process according to pathological evaluation. This novel curcumin oil solution may provide a new choice for PD prevention as a dietary supplement or clinically assisted treatment based on its better bioavailability and efficiency.

Glyphosate-induced gut microbiota dysbiosis facilitates male reproductive toxicity in rats.

Glyphosate (GLY), a ubiquitous environmental pollutant, can result in gut microbiota dysbiosis intimately involving various diseases. The latest research has shown an association between gut microbiota alteration and defective spermatogenesis. Here, we aimed to investigate whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity. Data showed that GLY-exposed rats exhibited male reproductive dysfunction, evidenced by impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio. 16S rDNA sequencing analysis indicated that GLY exposure altered the composition of gut commensal microbiota, of which the relative abundance of Bacteroidetes and Firmicutes phyla was significantly changed. Unexpectedly, the increased abundance of Prevotella_1 and Bacteroides genera was negatively correlated with sperm quality. Mechanistically, the pathological changes in GLY-exposed testis were accompanied by the increased interleukin (IL)-17A production, probably due to gut microbes-derived Th17 cell migration. Furthermore, activation of IL-17A signaling triggered testicular oxidative damage. Taken together, these findings uncover an underlying mechanistic scenario that gut microbiota dysbiosis-driven local IL-17A production is one reason responsible for male reproductive toxicity induced by GLY, which provides new insights into the male reproductive toxicity of GLY in mammals.

Glyphosate damages blood-testis barrier via NOX1-triggered oxidative stress in rats: Long-term exposure as a potential risk for male reproductive health.

Blood-testis barrier (BTB) creates a privileged niche indispensable for spermatogenesis. Glyphosate (GLY), the most commonly used herbicide worldwide, has been reported to decrease sperm quality. However, whether and how GLY destroys the BTB to affect sperm quality remains to be elucidated. Herein, this study was designed to investigate the influence of GLY on the BTB in vivo and in vitro experiments. The results showed that male rats exposed to GLY for 4 months exhibited a decrease in sperm quality and quantity, accompanied by BTB integrity disruption and testicular oxidative stress. Additionally, GLY-induced reactive oxygen species (ROS) contributed to the downregulation of BTB-related proteins in primary Sertoli cells (SCs). Intriguingly, we identified a marked upregulation of oxidative stress-related gene NOX1 in GLY-exposed testis based on transcriptome analysis. NOX1 knockdown blocked the GLY-induced oxidative stress, as well as prevented BTB-related protein decrease in SCs. Furthermore, the estrogen receptor (ER)-α was significantly upregulated in vivo and in vitro models. An ER-α inhibitor decreased the expression levels of both ER-α and NOX1. Mechanistically, GLY directly interacted with ER-α at the site of Pro39 and Lys401 to promote ER-α activation, which boosted NOX1 expression to trigger ROS accumulation. Collectively, these results demonstrate that long-term GLY exposure adversely affects BTB integrity, which disrupts spermatogenesis via activation of ER-α/NOX1 axis. This study presents a better understanding of the risk of long-term GLY exposure to male fertility.

Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder.

Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team's previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood. Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway. Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting. Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior. Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.

Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway.

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

Antifibrotic effect of Gancao Ganjiang decoction is mediated by PD-1 / TGF-ß1 / IL-17A pathway in bleomycin-induced idiopathic pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Firstly prescribed in the ancient Chinese book Jingui Yaolue, Gancao Ganjiang decoction (GGD) is a traditional Chinese herbal formula that has been widely used to treat "atrophic lung disease". GGD is a popular and widely used traditional Chinese medicine. The decoction is extracted from the dried rhizomes and roots of Glycyrrhiza uralensis Fisch. and Zingiber officinale Roscoe (2:1). AIM OF STUDY: To investigate the therapeutic effect of idiopathic pulmonary fibrosis (IPF) of GGD, a bleomycin-induced IPF murine model was used in this study. MATERIALS AND METHODS: Mice were induced by bleomycin instillation and GGD was orally administered. Changes on mice weight were recorded during the experiment. Lung weight was recorded on days 14 and 28, and pulmonary index was calculated accordingly. Pathological evaluation, including fibrosis analysis of lung tissue, was assessed by H&E and Masson staining. The expression of PD-1, p-STAT3 and IL-17A were detected by immunohistochemistry (IHC). The expression of p-STAT3 in lung tissues of mice were detected by Western blot. The level of IL-17A in lung tissue were detected by ELISA. The expression of PD-1 in CD4+ T cells in peripheral blood of mice was detected by flow cytometry. The levels of hydroxyproline and TGF-ß1 in lung tissue were detected by ELISA. The expression of E-cadherin, vimentin and α-SMA in lung tissues of mice were detected by qRT-PCR and Western blot. RESULTS: GGD can increase body weight and reduce pulmonary index in mice with pulmonary fibrosis. As such, GGD can significantly improve the inflammatory and alleviate IPF in the lung tissue of mice. GGD treatment was capable of reducing the content of PD-1 in lung tissue as well as the expression of PD-1 in CD4+ T cells in peripheral blood. Likewise, GGD was able to reduce the content of p-STAT3, IL-17A and TGF-ß1. In addition, GGD stimulation could inhibit epithelial-mesenchymal transformation (EMT) by increasing the expression of E-cadherin and reducing vimentin and α-SMA, thus reducing extracellular matrix (ECM) deposition. CONCLUSION: Our results indicate that GGD positively affects IPF by regulating PD-1/TGF-ß1/IL-17A pathway.

Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference.

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In the present study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference (CPP) experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal dopamine (DA), 5-hydroxytryptamine (5-HT), and endorphins (ß-EP) and serum interleukin (IL)-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and ß-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and ß-EP and lowering the IL-1α and IL-2 concentrations.

The benzoate plant metabolite ethyl gallate prevents cellular- and vascular-lipid accumulation in experimental models of atherosclerosis.

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.

Quercetin alleviates Cadmium-induced autophagy inhibition via TFEB-dependent lysosomal restoration in primary proximal tubular cells.

Autophagy dysregulation plays a pivotal role in cadmium (Cd)-induced nephrotoxicity. Quercetin (Qu), a flavonoid antioxidant with autophagy-enhancing effect, has protective effect on Cd-induced toxicity, but whether it can prevent Cd-induced nephrotoxicity via restoration of autophagy remains unknown. Here, primary rat proximal tubular (rPT) cells were exposed to Cd and/or Qu in vitro to clarify this issue. Data first showed that Cd-impaired autophagic flux was markedly alleviated by Qu, including decreased levels of autophagy marker proteins and recovery of autophagosome-lysosome fusion targeted for lysosomes. Meanwhile, Cd-induced lysosomal alkalization due to v-ATPases inhibition was prominently recovered by Qu. Accordingly, Qu enhanced Cd-diminished lysosomal degradation capacity and lysosome-related gene transcription levels. Notably, Qu improved Cd-inhibited TFEB nuclear translocation and its gene transcription level. Furthermore, data showed that the restoration of Cd-impaired autophagy-lysosome pathway and resultant alleviation of cytotoxicity by Qu are TFEB-dependent using TFEB gene silencing and overexpression technologies. In summary, these data provide novel evidences that the protective action of Qu against Cd-induced autophagy inhibition is attributed to its restoration of lysosomal dysfunction, which is dependent on TFEB.

Inhalation Administration of Agarwood Incense Rescues Scopolamine-Induced Learning and Memory Impairment in Mice.

Background: Agarwood, a type of herbal medicine widely used in Asian countries, is noted in traditional medicine for its intelligence-enhancing effects. Agarwood incense is traditionally administered by oral and nasal inhalation. To verify whether agarwood incense can exert its intelligence-enhancing effects in this way to rescue learning and memory impairment, typical clinical manifestations of dementia, we conducted a set of behavioral tests related to learning and memory. Methods: C57BL/6 mice were divided into six groups. In addition to the control and model groups, we added a donepezil treatment group to evaluate the effect of three different agarwood administration doses. After a week of administration, scopolamine was injected 30 min before each behavioral test to create a learning and memory impairment model. A series of behavioral tests [the Morris water maze test (MWM), the novel object recognition test (NOR), and the step-down test (SDT)] were used to assess their learning ability, as well as their spatial and recognition memory. Results: After scopolamine injection, the model group showed significant learning and memory impairment (i.e., longer latencies, lower crossing times, and lesser distance travelled in the target quadrant in MWM; a lower recognition index in NOR; and longer latencies and higher error times in SDT). The other four treatment groups all showed improvements in these indicators, and the overall therapeutic effect of agarwood was superior. Conclusion: The inhalation administration of agarwood can significantly improve the learning and memory impairment caused by scopolamine in mice, and the therapeutic effect varied between doses.