[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

[Research progress of Shegan Mahuang Decoction and predictive analysis on its Q-markers].

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.

[Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway].

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

[Review of chemical composition, pharmacological effects, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma and prediction of its Q-markers].

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.

ABCB1 Gene Is Associated With Clinical Response to SNRIs in a Local Chinese Han Population.

Background: The relation between the ATP-binding cassette subfamily B member 1 (ABCB1) gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 (G2677T) and rs1128503 (C1236T) single-nucleotide polymorphisms (SNPs) of ABCB1 but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population. Methods: The study population included 292 patients with MDD. All patients were assessed at baseline and at first, second, fourth, and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAM-D17) to determine their therapeutic responses to SSRIs and SNRIs. Results: In the SSRI therapy group, the genotype or allele distribution of six SNPs was not significantly different between responders and nonresponders. In the SNRI therapy group, only rs2032583 was associated with a therapeutic response to SNRIs. The C allele of the ABCB1 rs2032583 polymorphism was negatively correlated with therapeutic responses according to logistic regression analysis. Conclusion: The ABCB1 gene polymorphisms may not be associated with therapeutic responses to SSRIs but not with SNRIs. The TT genotype of rs2032583 could be a predictive factor of improved treatment responses to SNRIs in the Chinese population. These findings should be replicated in future studies with larger patient groups.

Effects of Aspirin in Rats With Ouabain Intracerebral Treatment-Possible Involvement of Inflammatory Modulation?

Bipolar disorder (BD) is a chronic and refractory disease with high probability of morbidity and mortality. Although epidemiological studies have established a strong association between BD and immune dysfunction, the precise etiology is still debatable, and the underpinning mechanism remains poorly investigated and understood. In the present study, manic-like symptoms of BD were induced in rats after intracerebroventricular administration of ouabain. Aspirin, a commonly used anti-inflammatory agent, was used to treat the induced manic-like symptoms and inflammation. Concentrations of a spectrum of inflammatory cytokines were examined by enzyme-linked immunosorbent assay in both plasma and brain tissues, and expression of Toll-like receptors 3 and 4 were determined in rat brains. Locomotor activity was monitored with open-field test to assess the effects of ouabain challenge and to evaluate the treatment efficacy of aspirin. Ouabain administration recapitulated many mania-like features such as increased stereotypic counts, traveling distance in open-field test, and decreased expression of brain-derived neurotrophic factor, interferon gamma, and Toll-like receptor 3, which were frequently found in patients with BD. These abnormalities could be partially reversed by aspirin. Our findings suggest that aspirin could be used as a promising adjunctive therapy for BD.

Increased frontal gray matter volume in individuals with prodromal psychosis.

BACKGROUND: Brain anatomical deficits associated with cognitive dysfunction have been reported in patients with schizophrenia. However, it remains unknown whether such anatomical deficits exist in individuals with prodromal psychosis. The present study is designed to investigate anatomical deficits in prodromal individuals and their associations with clinical/cognitive features. METHODS: Seventy-four prodromal individuals and seventy-six healthy controls were scanned using structural magnetic resonance imaging. Support vector machines were applied to test whether anatomical deficits might be used to discriminate prodromal individuals from healthy controls. RESULTS: Prodromal individuals showed significantly increased gray matter volume (GMV) in the right inferior frontal gyrus (IFG) and right rectus gyrus relative to healthy controls. No correlations were observed between increased GMV and clinical/cognitive characteristics. The combination of increased GMV in the right rectus gyrus and right IFG showed a sensitivity of 74.32%, a specificity of 67.11%, and an accuracy of 70.67% in differentiating prodromal individuals from healthy controls. CONCLUSION: Our results provide evidence of increased frontal GMV in prodromal individuals. A combination of GMV values in the two frontal brain areas may serve as potential markers to discriminate prodromal individuals from healthy controls. The results thus highlight the importance of the frontal regions in the pathophysiology of psychosis.

Immunological effects of refolded human soluble BAFF synthesized in Escherichia coli on murine B lymphocytes in vitro and in vivo.

The B cell activating factor of the TNF family (BAFF, also known as BLyS, TALL-1, THANK, and zTNF4) is an important survival factor for B lymphocytes. Our previous study has demonstrated that the final purified material of human soluble BAFF (refolded hsBAFF) synthesized in Escherichia coli is biologically active in a validated induced human B lymphocyte proliferation bioassay. In this study, the administration of refolded hsBAFF to isolated mouse B lymphocytes and mice was carried out to study the immunological effects of hsBAFF on in vitro and in vivo B lymphocytes. The results showed that splenic B lymphocyte proliferation significantly increased after hsBAFF administration (in vitro 1, 2, 3, 5 microg/ml and in vivo 0.01, 0.5, 1.0 mg/kg body mass). An oppositely elevated immune response of B lymphocyte to LPS stimulation after hsBAFF administration (1, 2.5, 5 microg/ml) and a significantly elevated change after treatment with hsBAFF and costimulation with anti-IgM (2.5 microg/ml) was observed in vitro, respectively. A similar change existed also in hsBAFF-treated mice on the 8th postexperiment day, but the value with anti-IgM alone didn't increase compared to normal control in vitro. We found that the treatment of mice with hsBAFF resulted in a developmental maturation of T1 B lymphocytes to T2 and mature B lymphocytes by detecting distributions of splenic CD21(lo) with CD45R/B220(+) and CD21(hi) with CD45R/B220(+) subsets. These results suggest that the refolded hsBAFF synthesized in Escherichia coli may enhance immune responses in the body by regulating the proliferation, differentiation, and immune response of B lymphocytes.

BAFF enhances B-cell-mediated immune response and vaccine-protection against a very virulent IBDV in chickens.

Infectious bursal disease (IBD) is an acute, highly infectious and immunosuppressive disease caused by IBDV, which specifically targets destruction of B cells in the bursa of Fabricius. B-cell activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, THANK, or zTNF4) is an important factor for B-cell proliferation and survival. Here we demonstrate that human soluble BAFF (hsBAFF) may enhance humoral immune response by elevating B lymphocyte activity of secretion of immunoglobulin (Ig) such as IgA, IgM and IgG in chickens immunized or unimmunized with an inactivated IBDV vaccine from a very virulent strain. Of importance, we found that hsBAFF, as a co-immunostimulant for vaccination, may play a vital role in amplifying the specific protective immune response, thereby potently preventing very virulent IBDV challenge. This is supported by serological evidence that hsBAFF may effectively enhance higher specific IgG activity and titre in serum of immunized chickens. The findings strongly suggest that BAFF may be exploited in combination with specific vaccination for prevention of IBD.

[Effects of splenic B lymphocyte proliferation and response and intracellular Ca2+ of hsBAFF in mice].

AIM: To investigate effects of hsBAFF synthesized in Escherichia coli on spleen B lymphocyte immune response and its intracellular free Ca2+ ([Ca2]i]) signaling in mice. METHODS: Twenty ICR mice, half males-half females, were chosen and randomly divided into a normal control group (n=10) and a hsBAFF treatment group (n-10). The mice in hsBAFF treatment group were given abdominal cavity injection of hsBAFF solution which was diluted with phosphate buffered saline (PBS) at dosage of 0.1 mg/kg body weight once each day for over eight days. The mice in control group were received abdominal injection of PBS at the same dose and frequency. Spleen B lymphocyte proliferation and its immune response to LPS stimulation in mice were evaluated using an MTT assay, and change of spleen B lymphocyte [Ca2+]i was assayed under a laser scanning confocal microscope. RESULTS: B lymphocyte proliferation and its immune response to LPS stimulation were significantly higher in hsBAFF-treated mice than in control mice (P < 0.05). The B lymphocyte [Ca2+]i fluorescence intensity in hsBAFF-treated mice maintained at a relatively high level fluctuation, and its average intensity was significantly higher to that of control mice (P < 0.01), but change rate of the intensity was lower compared to that of control group. CONCLUSION: hsBAFF synthesized in Escherichia coli can enhance immune function in the body by increasing B lymphocyte proliferation and its immune response. hsBAFF-activated B lymphocyte function may be associated with increasing B lymphocytes [Ca2+]i.