Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Neuroprotective Properties of Ferulic Acid in Preclinical Models of Alzheimer's Disease: A Systematic Literature Review.

BACKGROUND: Alzheimer's disease (AD) is one of the most common diseases in the elderly, with a high incidence of dementia. The pathogenesis of AD is complex, and there is no unified conclusion and effective treatment in the clinic. In recent years, with the development of traditional Chinese medicine (TCM), researchers put forward the idea of prevention and treatment of AD based on TCM according to the characteristics of multi- target of TCM. Ferulic acid (FA), also known as 3-methoxy-4-hydroxycinnamic acid, is an active ingredient in TCM that inhibits ß-amyloid (Aß) aggregation and has antioxidant and anti-inflammatory effects. FA derivatives have been reported to have low toxicity, high biological activity, and high blood-brain barrier permeability. However, the multitarget of FA in the treatment of AD has not been systematically elucidated. OBJECTIVES: In this systematic review, we aimed to comprehensively assess the neuroprotective effects of FA and its derivatives on in vitro and in vivo AD models. METHODS: We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Baidu Academic, and Wanfang databases for relevant pre-clinical studies until November 2021. RESULTS: We identified studies that evaluated the efficacy of FA and its derivatives using relevant keywords. 864 studies were included, of which 129 were found in PubMed, 111 in CNKI, 454 in Baidu Academic, and 170 in Wanfang. Due to duplication between databases, and after applying the exclusion and inclusion criteria, 43 articles were selected. Thereafter, the abstracts of the 43 articles were reviewed. Finally, 21 articles were included in this review, including 11 in vivo, 5 in vitro, and 5 in vivo and in vitro studies. CONCLUSION: Previous studies have shown that FA or its derivatives have multiple therapeutic effects on AD models and can improve the symptoms of AD and resistance of AD cell models. FA and its derivatives have anti-Aß aggregation, antioxidant, antiinflammatory, and other effects and are potential drugs for the multi-targeted treatment of AD. The result of our study showed that FA and its derivatives have significant therapeutic effects on animal and cell models of AD, suggesting that they may be potential therapeutic drugs for patients with AD.

Relationship between the therapeutic potential of various plant-derived bioactive compounds and their related microRNAs in neurological disorders.

BACKGROUND: Neurological disorders, such as ischemic stroke, spinal cord injury, neurodegenerative diseases, and glioblastoma often lead to long-term disability and death. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs of approximately 22 nucleotides, known to participate in both normal and pathological development, making them ideal therapeutic targets for clinical intervention. Several recent studies have suggested that plant-derived bioactive compounds (PDBCs) can have anti-atherosclerosis, antioxidant, and anti-inflammatory effects by regulating miRNAs. Thus, miRNAs are novel targets for the action of PDBCs. PURPOSE: The aim of this review was to evaluate the current status of PDBCs targeted miRNAs by dissecting their development status through a literature review. METHODS: A manual and electronic search was performed for English articles available from inception up to June 2022 reporting PDBCs and their regulating relationship with miRNAs for the therapeutic potential of neurological disorders. Information was retrieved from scientific databases including PubMed, ScienceDirect, Web of Science, Google Scholar and Chemical Abstracts Services. Keywords used for the search engines were "miRNAs" AND "Plant-derived bioactive compounds" in conjunction with "(native weeds OR alien invasive)" AND "traditional herbal medicine". RESULTS: A total of 37 articles were retrieved on PDBCs and their related miRNAs in neurological disorders. These PDBCs from traditional herbal medicine may play a therapeutic role in neurological disorders in a variety of mechanisms by regulating the corresponding miRNAs. These mechanisms mainly include inhibiting oxidative stress, anti-neuroinflammation, anti-autophagy, and anti-apoptosis. PDBC are a group of chemically distinct compounds derived from medicinal plants, some of which have therapeutic effects on neurological disorders. CONCLUSION: The emergence of miRNAs as pathological regulatory factors provides a new direction for the study of bioactive compounds in Traditional Chinese medicine and the elucidating of their epigenetic effects. Elucidating the regulatory relationship between bioactive compounds and miRNAs may help to identify new therapeutic targets and promoting the application of these compounds in precision medicine through their targeted molecular activity.

Ferulic acid: An extraordinarily neuroprotective phenolic acid with anti-depressive properties.

BACKGROUND: Depression, one of the most common mental illnesses and mood disorder syndromes, can seriously harm physical and mental health. As the pathophysiology of depression remains unclear, there is a need to find novel therapeutic agents. Ferulic acid (FA), a phenolic compound found in various Chinese herbal medicines, has anti-inflammatory and free radical scavenging properties as well as a wide range of therapeutic effects against depression. PURPOSE: In this review, we appraised preclinical research to fully discuss the anti-depression capacity of FA and discussed FAs' holistic characteristics that can contribute to better management of depression. STUDY DESIGN: We reviewed the results of in vitro and in vivo experiments using FA to treat depression and explored the possible antidepressant pharmacological mechanisms of FA for the clinical treatment of depression. METHODS: Electronic databases, including PubMed, Google Scholar, and China National Knowledge Infrastructure, were searched from the beginning of the database creation to December 2021. RESULTS: Studies on the antidepressant effects of FA show that it may exert such effects through various mechanisms. These include the following: the regulation of monoamine and non-monoamine neurotransmitter levels, inhibition of hypothalamic-pituitary-adrenal axis hyperfunction and neuroinflammation, promotion of hippocampal neurogenesis and upregulation brain-derived neurotrophic factor level, neuroprotection (inhibition of neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis), and downregulation of oxidative stress. CONCLUSION: Preclinical studies on the antidepressant effects of FA were reviewed in this study, and research on the antidepressant mechanisms of FA was summarized, confirming that FA can exert antidepressant effects through various pharmacological mechanisms. However, more multicenter clinical case-control studies are needed to confirm the clinical efficacy of FA.

Erigeron breviscapus (Vant.) Hand-Mazz.: A Promising Natural Neuroprotective Agent for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive cognitive dysfunction and memory loss in the elderly, which seriously affects the quality of their lives. Currently, the pathogenesis of AD remains unclear. Molecular biologists have proposed a variety of hypotheses, including the amyloid-ß hypothesis, tau hyperphosphorylation hypothesis, cholinergic neuron injury, inflammation caused by an abnormal immune response, and gene mutation. Drugs based on these pathological studies, including cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, have achieved a certain level of efficacy but are far from meeting clinical needs. In the recent years, some important advances have been made in the traditional Chinese medicine treatment of AD. Erigeron breviscapus (Vant.) Hand-Mazz. (EBHM) is an important medicinal plant distributed in Yunnan Province, China. Studies have shown that EBHM and its active ingredients have a variety of pharmacological effects with good therapeutic effects and wide application prospects for cognitive disability-related diseases. However, to our best knowledge, only few review articles have been published on the anti-AD effects of EBHM. Through a literature review, we identified the possible pathogenesis of AD, discussed the cultivation and phytochemistry of EBHM, and summarized the pharmacological mechanism of EBHM and its active ingredients in the treatment of AD to provide suggestions regarding anti-AD therapy as well as a broader insight into the therapeutic potential of EBHM.

Effects of Chaihu-Shugan-San for reflux esophagitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Reflux esophagitis (RE) is a common disease which is caused by the reflux of stomach and duodenal contents. As a classic prescription of traditional Chinese medicine, Chaihu-Shugan-San (CSS) has been used in the treatment of RE. However, no critically designed overview to evaluate the systematic review of CSS for RE has been carried out. The purpose of this study is to evaluate the efficacy and safety of CSS in the treatment of RE. METHODS AND ANALYSIS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, EMBASE, MEDLINE, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Bio-medicine Database, and VIP Chinese Periodical Database. Study selection, data extraction, and assessment of the risk of bias will be performed by 2 reviewers independently. Revman software (v.5.3) will be used to perform the meta-analyses. RESULTS: This study will provide a comprehensive evaluation of the efficacy and safety of CSS for patients with RE. CONCLUSION: The findings will be an available reference to evaluate the efficacy and safety of CSS on RE and provide decision-making reference on which method to choose for clinicians. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/5398R.

Paeoniflorin promotes angiogenesis and tissue regeneration in a full-thickness cutaneous wound model through the PI3K/AKT pathway.

The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients' need for functional and aesthetically pleasing scars. For the wound healing process, new blood vessels which can deliver nutrients and oxygen to the wound area are necessary. In this study, we investigated the pro-angiogenesis ability and mechanism in wound healing of paeoniflorin (PF), which is a traditional Chinese medicine. In our in vitro results, the ability for proliferation, migration and in vitro angiogenesis in human umbilical vein endothelial cells was promoted by coculturing with PF (1.25-5 µM). Meanwhile, molecular docking studies revealed that PF has excellent binding abilities to phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT), and consistent with our western blot results, that PF suppressed PI3K and AKT phosphorylation. Furthermore, to investigate the healing effect of PF in vivo, we constructed a full-thickness cutaneous wound model in rats. PF stimulated the cellular proliferation status, collagen matrix deposition and remodeling processes in vitro and new blood vessel formation at the wound bed resulting in efficient wound healing after intragastric administration of 10 mg·kg-1 ·day-1 in vivo. Overall, PF performed the pro-angiogenetic effect in vitro and accelerating wound healing in vivo. In summary, the capacity for angiogenesis in endothelial cells could be enhanced by PF treatment via the PI3K/AKT pathway in vitro and could accelerate the wound healing process in vivo through collagen deposition and angiogenesis in regenerated tissue. This study provides evidence that application of PF represents a novel therapeutic approach for the treatment of cutaneous wounds.

Skin hyperpigmentation: a rare presenting symptom of nitrous oxide abuse.

Context: Recreational nitrogen oxide (N2O) abuse can cause nervous system damage. There was a sharp increase in the number of patients with neurological disorders associated with recreational N2O use in China, as recreational N2O use became popular in young people nationwide. Among cases with neurological disorders caused by N2O abuse, a few showed skin hyperpigmentation, which has rarely been reported. We explored the characteristics of hyperpigmentation in N2O abusers to draw the attention of clinicians to this rare cutaneous symptom related to N2O abuse.Methods: We retrospectively collected data of patients with neurological disorders related to recreational N2O abuse in Shengjing Hospital of China Medical University from January 2014 to June 2019. Detailed clinical data were gathered from patients who manifested skin pigmentation, including the history of N2O abuse and characteristics of neurological lesions and skin pigmentation.Results: In total, 66 patients (average age: 22.7 ± 4.5 years, 36 males) with neurological disorders due to N2O abuse were included; four of them (17-23 years old, 1 male) manifested skin hyperpigmentation. The duration of N2O abuse of the four patients ranged from 2 to 24 months, and they all had peripheral neuropathy; the two patients also had subacute combined degeneration of the spinal cord. One patient exhibited significant hyperpigmentation throughout the body (trunk, limbs, and face), with no abnormalities in cortisol and other biochemical tests. One patient presented with punctuate pigmentation throughout the trunk. Two patients presented with finger skin pigmentation, especially in the distal phalanxes. Pigmentation after N2O use remitted slowly with vitamin B12 supplementation.Conclusion: Skin hyperpigmentation is a rare symptom in N2O abusers, which can distribute locally in hands or diffusely throughout the body. Therefore, attention should be paid to a history of N2O abuse and serum vitamin B12 level should be tested.

Duration of the flaxseed diet promotes deposition of n-3 fatty acids in the meat and skin of Peking ducks.

BACKGROUND: Polyunsaturated fatty acids (PUFA), particularly n-3, have beneficial effects on human health, and for this reason foodstuffs with increased content of n-3 PUFA are now very common and widely available. DESIGN: This study was conducted to investigate the effect of the duration of a flaxseed diet on Peking duck's growth performance, antioxidant status, gene expression, and fatty acid profile of the meat. A total of 792 12-day-old white Peking ducks were divided into four groups. In the control group, animals were provided with a basal diet. In the three experimental groups, animals were fed a 10% flax seed diet with vitamin E at 13, 23, and 33 days of age for 30, 20, and 10 days, respectively. RESULTS: The growth performance of the ducks decreased with flaxseed diet's duration. Both body weight and body weight gain decreased linearly while Feed conversion ratios (FCR) increased in the group of ducks fed flaxseed compared to control ducks. Serum triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST) linearly decreased while high density lipoprotein cholesterol (HDL-C) and lipopolysaccharide (LPS) levels increased by feeding flaxseed up to 30 days. The expression of lipin-1 gene (LPIN-1) and fatty acid desaturase 2 (FADS2) linearly increased in ducks fed flaxseed for 30 days. Linolenic acid (n-3) and its long-chain metabolites like eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 fatty acids (FA) linearly increased while the ratio of n-6 to n-3 was reduced with increased duration of flaxseed supplementation. CONCLUSION: Overall, we found that increasing the duration of flaxseed diet with vitamin E for more than 10 days had a mild adverse effect on duck's growth performance but enrichedits meat with long-chain PUFA and decreased the n-6 to n-3 ratio, providing quality meat for health-conscious consumers. A period of 20 days is good for producing n-3 enriched Peking duck meat and skin.

Influence of starch sources and dietary protein levels on intestinal functionality and intestinal mucosal amino acids catabolism in broiler chickens.

BACKGROUND: There is growing interest in carbohydrate and protein nutrition to enhance the efficiency of animal production. Reduced-crude protein diets depress environmental pollution and feeding cost, but the challenge to their adoption is maintaining digestive function and growth performance of birds. The present study was conducted to evaluate the influence of different dietary starch sources and protein levels on intestinal functionality and mucosal amino acid catabolism. METHODS: Six dietary treatments, based on maize and soybean meal, were offered to 360 AA+ male chicks from 6 to 35 d post-hatch as a 3 × 2 factorial array. Either waxy rice or amylose was added to a conventional maize-soy diet to provide three sources of starch with different digestion rates and relatively high and low dietary protein levels. Growth performance, parameters of intestinal functionality and concentrations of free amino acid in the portal circulation were determined. RESULTS: In the grower phase, starch source influenced (P < 0.02) weight gain as diets containing amylose supported significantly higher weight gains than waxy rice. Significant increase of ileal ATP concentrations and Na+/K+-ATPase activity were found in amylose treatment. Also, amylose decreased BrdU positive cell numbers and down-regulated mRNA expression for CASP-3. GOT activity in the ileum was higher (P < 0.01) in birds offered low protein diets and there was a trend (P = 0.057) for waxy rice as a starch source to increase ileal GOT activities. There was a significant influence on the concentration of seventeen amino acids in the portal circulation with tryptophan the one exception. Waxy rice as a starch source generated 13.6% and 22.4% numerically higher concentrations of non-essential amino acids than maize and amylose, respectively. CONCLUSIONS: Amino acid catabolism in the gut mucosa is subject to nutritional regulation. Given that amino acids can be spared from catabolism in the gut mucosa by supplementation of amylose, it follows their post-enteral availability would be improved and intestinal energy would be derived more efficiently from glucose.

Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature.

Purpose The abuse of nitrous oxide (N2O) can induce Vitamin B12 deficiency that subsequently leads to central nervous demyelination, myelopathy and peripheral neuropathy. Although myelopathy has been reported in the past, the specific locations and prognosis of the disease are still unclear. MATERIALS AND METHODS: We report the case of a 22-year-old male who presented with quadriplegia that began after a 3-month history of inhalation of N2O. We summarized the clinical data of this entity and performed a comprehensive literature review of various presentations and MRI features of myelopathy secondary to N2O abuse. RESULTS: In combination with previous reports of 14 cases, we found that the onset of the disease was usually subacute, and the majority of patients (92.85%) were young men. There was no definite relationship between myelopathy and the amount or duration of N2O inhalation. The most common clinical manifestation was sensory ataxia, and the cervical spinal cord was the most frequently impaired area of the whole spinal cord. The spinal cord lesions had a high signal intensity on T2-weighted MRI and usually involved more than three spinal segments and impaired the posterior column more significantly. Most patients recovered well after vitamin B12 supplementation. CONCLUSIONS: Myelopathy secondary to N2O abuse is generally seen in young men. The clinical diagnosis mainly depends on a history of N2O inhalation and the characteristic imaging changes in the posterior cervical spinal cord. Early diagnosis and intervention are important for a satisfactory prognosis.

Evaluation of four commonly used DNA barcoding Loci for chinese medicinal plants of the family schisandraceae.

Many species of Schisandraceae are used in traditional Chinese medicine and are faced with contamination and substitution risks due to inaccurate identification. Here, we investigated the discriminatory power of four commonly used DNA barcoding loci (ITS, trnH-psbA, matK, and rbcL) and corresponding multi-locus combinations for 135 individuals from 33 species of Schisandraceae, using distance-, tree-, similarity-, and character-based methods, at both the family level and the genus level. Our results showed that the two spacer regions (ITS and trnH-psbA) possess higher species-resolving power than the two coding regions (matK and rbcL). The degree of species resolution increased with most of the multi-locus combinations. Furthermore, our results implied that the best DNA barcode for the species discrimination at the family level might not always be the most suitable one at the genus level. Here we propose the combination of ITS+trnH-psbA+matK+rbcL as the most ideal DNA barcode for discriminating the medicinal plants of Schisandra and Kadsura, and the combination of ITS+trnH-psbA as the most suitable barcode for Illicium species. In addition, the closely related species Schisandra rubriflora Rehder & E. H. Wilson and Schisandra grandiflora Hook.f. & Thomson, were paraphyletic with each other on phylogenetic trees, suggesting that they should not be distinct species. Furthermore, the samples of these two species from the southern Hengduan Mountains region formed a distinct cluster that was separated from the samples of other regions, implying the presence of cryptic diversity. The feasibility of DNA barcodes for identification of geographical authenticity was also verified here. The database and paradigm that we provide in this study could be used as reference for the authentication of traditional Chinese medicinal plants utilizing DNA barcoding.

[Impacts of rotating or lifting-thrusting manipulation on distant vision of naked eye in patients of juvenile myopia: a randomized controlled trial].

OBJECTIVE: To compare the differences in the efficacy on distant version of naked eye in the patients of juvenile myopia between rotating manipulation and lifting-thrusting manipulation of acupuncture. METHODS: One hundred and twenty cases (240 eyes) were randomized into a rotating manipulation group and a lifting-thrusting manipulation group, 60 cases (120 eyes) in each group. Additionally, a corrective lenses group, 60 cases (120 eyes), was set up as the control. In both manipulation groups, Cuanzhu (BL 2),Yuyao (EX-HN 4), Sizhukong (TE 23), Taiyang (EX-HN 5), Fengchi (GB 20), Zusanli (ST 36), Guangming (GB 37) and Sanyinjiao (SP 6) were punctured, but stimulated with rotating manipulation and lifting-thrusting manipulation respectively three times per week, 10 times as a treatment session and totally one session was required. In the corrective lenses group, the glasses were applied at daytime. The clinical efficacy and the changes in distant vision of naked eye before and after treatment were compared among the three groups. RESULTS: The total effective rate was 87.5% (105/120) in the rotating manipulation group, which was better than 69.2% (83/120) in the lifting-thrusting manipulation group (P < 0.05). The distant vision of naked eye was improved apparently in the rotating manipulation group and the lifting-thrusting manipulation group after treatment (both P < 0.05). But it was not improved in the corrective lenses group (P > 0.05). The distant vision of naked eye was improved more apparently after treatment in the rotating manipulation group as compared with that in the lifting-thrusting manipulation group (0.75 +/- 0.23 vs 0.68 +/- 0.24, P < 0.05). For 96 cases (192 eyes) with acupuncture treatment, in 3-month follow-up, 87.0% (167/192) of the cases maintained the stable vision as the original level and 13.0% (25/192) of them were reduced in the vision In the acupuncture groups, it was found that the improvement of distant vision of naked eye was more obvious after treatment with younger age, better basic vision and shorter duration of sickness (all P < 0.05). CONCLUSION: Acupuncture achieves the positive and sustainable clinical effect on juvenile myopia, and the results of rotating manipulation are superior to that of lifting-thrusting manipulation. Age, basic vision and duration of sickness impact the clinical efficacy.