Efficacy of Chinese herbal formula Kai-Xin-San on rodent models of depression: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS, or Happy Feeling Powder), a typical Chinese herbal prescription, is frequently used for treating depression by the multi-level and multi-target mechanism. AIM OF THE STUDY: To systematically investigate the efficacy and safety of KXS on depression in preclinic trials. MATERIALS AND METHODS: We independently searched for preclinical animal studies of KXS on depression from inception to June 28, 2022, using electronic databases, e.g., PUBMED. The measurements were performed to assess the outcomes of behavioral tests. RESULTS: This systematic review and meta-analysis included twenty-four studies and 608 animals. A remarkable effect of KXS in depression behavioral tests, including sucrose consumption test (SMD: 2.36, 95% CI: (1.81, 2.90); Z = 8.49, P < 0.00001)., forced swimming test (MD = -60.52, 95% CI: (-89.04, -31.99); Z = 4.16, P < 0.0001), rearing times (MD=4.48, 95% CI: (3.39, 5.57); Z = 8.05, P < 0.00001) and crossing times (MD = -33.7, 95% CI: (25.74, 41.67); Z = 8.29, P < 0.00001) in the open field test, showing KXS's excellent efficiency in improving depressive-like symptoms of animals. CONCLUSIONS: Our meta-analysis showed KXS remarkably relieved animals' depressive-like symptoms, providing evidence that KXS can be a promising drug candidate for depression treatment.

Antidepressant effects of the traditional Chinese herbal formula Xiao-Yao-San and its bioactive ingredients.

BACKGROUND: Depression is one of the most debilitating and severe psychiatric disorders and a serious public health concern. Currently, many treatments are indicated for depression, including traditional Chinese medicinal formulae such as Xiao-Yao-San (XYS), which has effective antidepressant effects in clinical and animal studies. PURPOSE: To summarize current evidence of XYS in terms of the preclinical and clinical studies and to identify the multi-level, multi-approach, and multi-target potential antidepressant mechanisms of XYS and active components of XYS by a comprehensive search of the related electronic databases. METHODS: The following electronic databases were searched from the beginning to April 2022: PubMed, MEDLINE, Web of Science, Google Scholar, and China National Knowledge Infrastructure. RESULTS: This review summarizes the antidepressant mechanisms of XYS and its active ingredients, which are reportedly correlated with monoamine neurotransmitter regulation, synaptic plasticity, and hypothalamic-pituitary-adrenal axis, etc. CONCLUSION: XYS plays a critical role in the treatment of depression by the regulation of several factors, including the monoaminergic systems, hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, brain-gut axis, and other pathways. However, more clinical and animal studies should be conducted to further investigate the antidepressant function of XYS and provide more evidence and recommendations for its clinical application. Our review provides an overview of XYS and guidance for future research direction.

Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L., possessing multifaceted properties, e.g., antioxidant, anti-inflammatory, and enhancement of cognitive ability. Besides, it can cross the blood-brain barrier, thereby exerting a neuroprotective effect. However, so far, MGF's effect in balancing mitochondrial homeostasis via regulation of Drp1 level and mitophagic pathway in PD remains rarely reported. PURPOSE: We aimed to investigate the neuroprotective effect of MGF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and examine the possible mechanisms. METHODS: We utilized C57BL/6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Behavioral parameters, containing the open field test, balance beam, pole test, and rotarod test, assessed the locomotor activity; immunohistochemistry assessed the number of TH-positive neurons; transmission electron microscopy detected ultrastructural mitochondrial morphology in the dopaminergic neuron; complex I enzymatic activity microplate assay kit measured the mitochondrial complex I activity; ATP determination kit measured ATP levels in mitochondria isolated from cells or striatal tissues; western blot measured the levels of Drp1 and mitophagic proteins. RESULTS: We observed that MGF could mitigate motor deficiency and improve the expression of tyrosine hydroxylase in the substantia nigra of MPTP-induced PD mice. Furthermore, MGF not only ameliorated mitochondrial ultrastructure, but also improved mitochondrial ATP content. Within mitochondria, MGF could reduce Drp1 expression and reverse the expressions of mitophagic proteins, including PINK1, Parkin, NIX, BNIP3, FUNDC1, and p62. CONCLUSION: Present study indicates that MGF benefits mitochondrial networks by recovering mitochondrial ultrastructure and ATP contents, reducing mitochondrial Drp1, and modulating mitophagic proteins in the MPTP-induced PD mice model, which revealed a novel acting mechanism of MGF in PD's treatment.

Efficacy of paeoniflorin on models of depression: A systematic review and meta-analysis of rodent studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin, a bioactive compound extracted from the traditional Chinese herb, Paeonia lactiflora Pall, has been demonstrated to possess efficient antidepressant activity in previous studies. AIM OF THE STUDY: Our systematic review and meta-analysis aimed to assess the effectiveness of paeoniflorin in relieving depressive-like behaviors in animal models. MATERIALS AND METHODS: We searched for in vivo studies on the antidepressant effects of paeoniflorin in rodents using electronic databases from their inception to April 2021. The measurements of animal behavioral tests, including the sucrose consumption, forced swimming, tail suspension, and open field tests, were regarded as the outcomes. RESULTS: Fourteen studies involving 416 animals met the inclusion criteria and were included in the meta-analysis. Statistical analysis revealed remarkable differences between the paeoniflorin and control groups. Furthermore, the paeoniflorin group showed great efficiency in improving depressive-like symptoms of animals in the sucrose consumption, forced swimming, tail suspension, and open field tests. CONCLUSIONS: Our meta-analysis demonstrates that paeoniflorin can significantly improve depressive-like symptoms in animals and suggests that it can be a potential therapy for patients with depression in the future.

Canonical Chinese medicine formula Danzhi-Xiaoyao-San for treating depression: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi-Xiaoyao-San (DXS), as a canonical Chinese medicine formula, possessing the functions of the soothing liver, invigorating spleen, clearing heat, and cooling blood, has been widely used for the treatment of depression. AIM OF THE STUDY: This systematic review and meta-analysis of randomized controlled trials aimed to examine the efficacy of DXS in depression. MATERIALS AND METHODS: We performed a literature search in several databases, e.g., PUBMED, until August 2021 and conducted the meta-analysis using Review Manager 5.3 software. The random-effects model and fixed-effects model were used to synthetize extracted data. RESULTS: Finally, this meta-analysis showed that comparing with antidepressants, DXS exhibited similar effect to antidepressants in the clinical comprehensive effect [RR = 1.04, 95% CI (0.77, 1.40); P = 0.81] and decrease in Self-Rating Depression Scale scores [WMD = 0.89, 95% CI (-6.33, 8.11); P = 0.81], while lower effect in Hamilton Depression Scale scores [SMD = -0.29, 95% CI (-0.55, -0.03); P = 0.03]; Furthermore, DXS plus antidepressants can significantly improve the clinical comprehensive effect [RR = 1.23, 95% CI (1.17, 1.29); P < 0.00001] and decrease the Hamilton Depression Scale scores [SMD = 1.04, 95% CI (0.51, 1.58); P = 0.0001] than pure antidepressants. CONCLUSION: This systematic review and meta-analysis approved an efficient role of DXS in improving depression in clinical randomized controlled trials. However, further evidence from large samples and high-quality randomized controlled trials is needed to be investigated for a reliable conclusion about DXS in the treatment of depression.

Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties.

BACKGROUND: Depression, as a prevalent and debilitating psychiatric disease, severely decreases the life quality of individuals and brings heavy burdens to the whole society. Currently, some antidepressants are applied in the treatment of severe depressive symptoms, while there are still some undesirable drawbacks. Paeoniflorin is a monoterpenoid glycoside that was firstly extracted from Paeonia lactiflora Pall, a traditional Chinese herb that is widely used in the Chinese herbal formulas for treating depression. PURPOSE: This review summarized the previous pre-clinical studies of paeoniflorin in treating depression and further discussed the potential anti-depressive mechanisms for that paeoniflorin to be further explored and utilized in the treatment of depression clinically. METHODS: Some electronic databases, e.g., PubMed and China National Knowledge Infrastructure, were searched from inception until April 2021. RESULTS: This review summarized the effective anti-depressive properties of paeoniflorin, which is related to its functions in the upregulation of the levels of monoaminergic neurotransmitters, inhibition of the hypothalamic-pituitary-adrenal axis hyperfunction, promotion of neuroprotection, promotion of hippocampus neurogenesis, and upregulation of brain-derived neurotrophic factor level, inhibition of inflammatory reaction, downregulation of nitric oxide level, etc. CONCLUSION: This review focused on the pre-clinical studies of paeoniflorin in depression and summarized the recent development of the anti-depressive mechanisms of paeoniflorin, which approves the role of paeoniflorin plays in anti-depression. However, more high-quality pre-clinical and clinical studies are expected to be conducted in the future.

Efficacy of Traditional Chinese Medicine Combined with Selective Serotonin Reuptake Inhibitors on the Treatment for Parkinson's Disease with Depression: A Systematic Review and Meta-Analysis.

Depression is a common neuropsychiatric symptom of Parkinson's disease (PD), resulting in a lower quality of life and cognitive impairment in PD patients. Traditional Chinese medicine (TCM) formulas have been widely used in neurodegenerative disease and neuropsychic disorders to improve life quality of patients in ethnomedicine. TCM formulas combined with selective serotonin reuptake inhibitors (SSRIs) also have a positive effect on depressed PD compared with SSRIs as reported by several clinical studies. However, the results are discordant and failed to be conclusive. We aim to evaluate the efficacy of TCM formulas combined with SSRIs for depressed PD in this systematic review. We searched literatures from PubMed, Web of Science, Medline, Embase, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Information Database before July 2020. We included randomized controlled trials investigating the efficacy of TCM formulas combined with SSRIs on depressed PD patients. This analysis was according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Eleven randomized clinical trials involving 861 subjects were enrolled in this analysis. The overall results showed that TCM formulas combined with SSRIs significantly improved the depression score [weighted mean difference (WMD): -4.920, 95% confidence interval (CI): (-5.999, -3.840); [Formula: see text]¡ 0.001] and had a statistical significance on Unified Parkinson's Disease Rating Scale II score [WMD: -1.209, 95% CI: (-1.561, -0.857); [Formula: see text] < 0.001]. Furthermore, we observed that Chai-Hu-Shu-Gan Powder combined with SSRIs had a significant improvement on the depressive symptom in PD compared to the SSRIs alone [WMD: -5.390, 95% CI: (-7.66, -3.11); [Formula: see text] < 0.001]. No severe side events were reported in these included trials. This systematic review provided the evidences that TCM formulas combined with SSRIs might be helpful and safe in the treatment of depression of PD, including Chai-Hu-Shu-Gan Powder. Also, more randomized double-blinded trials with reliable design are required in the future.

[Role of hippocampus NMDAR subunits in electroacupuncture at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on gastric motility, protooncogene c-fos and hippocampus N-methyl-D-aspartate (NMDA) receptor subunits in rats with functional dyspepsia (FD), and to discuss the molecular mechanism of hippocampal in EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility. METHODS: Eighty-four Sprague Dawley (SD) rats were randomly divided into a normal group, a model group, a Zhongwan group, a Weishu group, an acupoint combination group and a non-acupoint group, 14 rats in each one. Except for the normal group, FD model were established by moderate tail-clipping infuriation method and irregular feeding. The rats in the Zhongwan group, Weishu group, acupoint combination group and non-acupoint group were treated with EA at corresponding acupoints, 20 min per treatment, once a day for 7 days. The rats in the normal group and the model group received no treatment; grabbing and fixation were applied in the model group. The stress transducer was used to record gastric motion waveforms; immunohistochemistry method was used to detect the expression of c-fos in hippocampus; Western blot method was used to detect the expression of NMDA receptor subunits NR1, NR2A and NR2B in hippocampus. RESULTS: Compared with the normal group, the gastric motility range was decreased (P<0.05), and the expression of hippocampus NR2A was reduced and the levels of NR1 and NR2B were increased in the model group (P<0.05), however, hippocampus c-fos expression was not significant different between the normal group and the model group (P>0.05). Compared with the model group, the gastric motility range was increased, the expression of hippocampus c-fos and expression of hippocampus NR2A was increased but expressions of NR1 and NR2B were reduced in the Weishu group, Zhongwan group and acupoint combination group (P<0.05). Besides, the differences of gastric motility range and expression of hippocampus c-fos, NR1, NR2A and NR2B between the model group and the non-acupoint were not significant (P>0.05). Compared with the Zhongwan group and the Weishu group, the gastric motility range was increased, the expression of hippocampus c-fos and NR2A was increased but the expression of NR1 and NR2B was reducedin the acupoint combination group (P<0.05). There was no significant difference in the frequency of gastric motility among the groups (P>0.05). CONCLUSION: EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) could increase gastric motility of FD rats, which is likely to be related with activating hippocampal neurons, upregulating the level of NR2A and downregulating NR1 and NR2B.

Overexpression of folate biosynthesis genes in rice (Oryza sativa L.) and evaluation of their impact on seed folate content.

Folate (vitamin B9) deficiency is a global health problem especially in developing countries where the major staple foods such as rice contain extremely low folates. Biofortification of rice could be an alternative complement way to fight folate deficiency. In this study, we evaluated the availability of the genes in each step of folate biosynthesis pathway for rice folate enhancement in the japonica variety kitaake genetic background. The first enzymes GTP cyclohydrolase I (GTPCHI) and aminodeoxychorismate synthase (ADCS) in the pterin and para-aminobenzoate branches resulted in significant increase in seed folate content, respectively (P < 0.01). Overexpression of two closely related enzymes dihydrofolate synthase (DHFS) and folypolyglutamate synthase (FPGS), which perform the first and further additions of glutamates, produced slightly increase in seed folate content separately. The GTPCHI transgene was combined with each of the other transgenes except ADCS to investigate the effects of gene stacking on seed folate accumulation. Seed folate contents in the gene-stacked plants were higher than the individual low-folate transgenic parents, but lower than the high-folate GTPCHI transgenic lines, pointing to an inadequate supply of para-aminobenzoic acid (PABA) precursor initiated by ADCS in constraining folate overproduction in gene-stacked plants.