Xiaoyaosan promotes neurotransmitter transmission and alleviates CUMS-induced depression by regulating the expression of Oct1 and Oct3 in astrocytes of the prefrontal cortex.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription for the treatment of liver depression and qi stagnation, and pharmacological studies have shown that XYS has great potential to reverse depression. However, anti-depression targets and the mechanism of XYS are still not entirely clear. AIM OF THE STUDY: The present study aims to explore and verify the anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant effect of XYS was assessed in rats with depression induced by chronic unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in different brain regions were measured using ELISA. The expression of organic cation transporters (Octs) were detected by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the correlation between Octs and depression-like behavior. Then, the effects of XYS on the behavior, neurotransmitter concentration, and Octs expression in D22-induced rats were examined. Finally, primary astrocytes were used to verify the mechanism of XYS exerting anti-depressant activity by regulating Octs. RESULTS: The result showed that XYS had a significant positive impact on the behavior of depression rats induced by CUMS. XYS also improved the secretion of 5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 expression in the PFC. These results suggest that XYS has the potential to alleviate depression by enhancing the secretion of neurotransmitters. This may be related to XYS regulation of Oct's expression. When the expression of Octs was inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was able to reverse this behavior, indicating that Octs play a significant role in the development of depression and XYS may exert its antidepressant effects through the regulation of Octs. Furthermore, the study also found that dopamine uptake decreased after inhibiting the expression of Octs, and XYS-containing serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant effects by promoting dopamine uptake to improve neurotransmitter transport by regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: The antidepressant effect of XYS may be attributed to its ability to regulate the expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting neurotransmitter transport.

Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy.

Psoriasis, a prevalent inherited skin condition, involves an inflammatory response as a key pathogenic mechanism. The Optimized Yinxieling Formula (OYF), rooted in traditional Chinese medicine, is extensively utilized in clinical settings to treat psoriasis. Although previous studies have demonstrated OYF's significant anti-inflammatory effects in psoriasis, its potential molecular targets and active components remain unexplored. This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF. Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators, including IL-23, nitric oxide, TNF-α, and IL-1ß, in LPS-induced RAW264.7 cells. We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy, known as Target Fishing. The enriched target proteins were subsequently identified via LC-MS/MS, followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network. We identified a total of 76 potential target proteins, which were highly associated with mRNA transcription mechanisms. In particular, pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract. We further utilized a target protein-based affinity capture strategy, combined with LC-MS and SPR analysis, to globally screen OYF's active components, focusing on the mRNA transcription regulator, fused in sarcoma (FUS). This process led to the identification of umbelliferone, vanillic acid, protocatechuic acid, gentisic acid, and echinacoside as key compounds targeting FUS to inhibit IL-23 expression. Additionally, we formulated a compound cocktail (CpdC), which significantly reduced psoriasis area and severity index (PASI) scores and the expressions of IL-23 and Ki67 in an imiquimod (IMQ)-induced psoriasis mouse model. Collectively, our study elucidates the primary molecular targets and active components of OYF, offering novel insights for psoriasis treatment.

Comparative Study on Volatile Oils among Bupleuri radix Species and Habitats: Yields, Chemical Characterization and Antipyretic Activities.

Volatile oils from several Bupleuri radix (BR) are reported as potential sources of drugs. To provide evidence for the application of BR, the volatile oils from 19 batches of different species and habitats of BR including Bupleurum chinese DC. (BCD), Bupleurum scorzonerifolium Willd. (BSW), Bupleurum bicaule Helm (BBH), Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y.Li (BMS), Bupleurum marginatum Wall.ex DC. (BMW) and Bupleurum falcatum L. (BFL) were investigated. The composition of BR volatile oils was determined by GC/MS. Samples were clustered by hierarchical cluster analysis (HCA). Fever was induced by Lipopolysaccharide (LPS), and antipyretic activities of BR volatile oils were evaluated with Chaihu injection (CI) as the positive control. The yields of volatile oils were among 360-5320 ppm. A total of 229 components were identified by GC/MS. Samples could be divided into 4 clusters by HCA. 4 representative samples, one for each cluster, were selected to further compare their antipyretic activities. For the highest content of volatile oil (5320 ppm) and the best activity, BSW has great potential for utilization.

Vinegar-baked Radix Bupleuri enhances the liver-targeting effect of rhein on liver injury rats by regulating transporters.

OBJECTIVE: This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury. METHODS: The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays. KEY FINDING: VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein. CONCLUSION: VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.

Integrating pharmacokinetics and network pharmacology to identify and validate targets of Guben Xiaozhen prescription for the treatment of chronic urticaria.

ETHNOPHARMACOLOGICAL RELEVANCE: Guben Xiaozhen prescription (GXP), a prescription of traditional Chinese medicine, has been used to treat skin diseases for a long history and achieved satisfactory therapeutic effects. However, its active ingredients and targets remain to be further elucidated. AIM OF THIS STUDY: Identify activity ingredients of GXP for the treatment of chronic urticaria (CU) and further validate the efficacy and targets of the selected component. MATERIALS AND METHODS: Firstly, the pharmacokinetics of different disassemble groups of GXP was investigated to screen for active ingredients with improved bioavailability. Then, shared targets between active ingredients and CU were performed by network pharmacology. Finally, the ovalbumin (OVA) induced CU model was used to verify the efficacy and targets of the screened active ingredient. RESULTS: Pharmacokinetic results showed that, compared with sub-division groups, the maximum concentration (Cmax) and blood concentration-time curve (AUC0-t) of eight ingredients, including 6-shogaol, 6-gingerol, calycosin, dictamnine, fraxinellone, schizandrin, cimifugin, and sec-o-glucosylhamaudol were increased in the GXP group. Then, 218 CU-related targets and 20 shared targets with six potential active compounds were screened by network pharmacology. Further analysis found that fraxinellone was not reported to be associated with CU in the literature. Therefore, the present study employed an OVA-induced CU model and found that fraxinellone could dose-dependently inhibit the locus coeruleus reaction, mast cell degranulation, and pathological skin damage. Moreover, we further verified the ADRB2 and its downstream target caspase3 predicted by network pharmacology, and fraxinellone inhibited the expression of ADRB2 and caspase3 in high dose group, suggesting that fraxinellone may play an anti-CU role by inhibiting inflammation and cell apoptosis. CONCLUSION: In this study, integrated pharmacokinetics and network pharmacology methods were established to screen out six effective active ingredients in GXP for the treatment of CU. This study provides a new idea for screening active substances in traditional Chinese medicine.

Comparative Characterization and Immunomodulatory Activities of Polysaccharides Extracted from the Radix of Platycodon grandiflorum with Different Extraction Methods.

Platycodon grandiflorum is an edible and medicinal plant, and polysaccharides are one of its important components. To further improve the utilization rate of P. grandiflorum, we investigated the effects of four different extraction methods, including hot water, ultrasonic-assisted, acid-assisted, and alkali-assisted extractions, on the polysaccharides, which were named PG-H, PG-U, PG-C, and PG-A. The findings indicated that the extraction method had a significant impact on the yield, characteristics, and immunoregulatory activity. We observed that the yields decreased in the following order: PG-H, PG-U, PG-C, and PG-A. Galacturonic acid, glucose, galactose, and arabinose were the most prevalent monosaccharides in the four PGs. However, their proportions varied. In addition, the difference between the content of glucose and galacturonic acid was more significant. PG-U had the highest glucose content, whereas PG-C had the lowest. Galacturonic acid content was highest in PG-A, while the lowest in PG-U. The molecular weight decreased in the order of PG-U, PG-H, PG-C, and PG-A; the particle size was in the order of PG-U, PG-A, PG-H, and PG-C. Moreover, the extraction method had a great impact on immunoregulatory activity. The ability to stimulate the immune function of macrophages was as follows: PG-A > PG-C > PG-U > PG-H. The results indicated that PGs, with lower molecular weights and higher GalA content, exhibited better immune-stimulating activity. And more important the AAE method was a good way to extract polysaccharides from Platycodon grandiflorum for use as a functional product and immunological adjuvant.

Application of uniform design to evaluate the different conditions on the growth of algae Prymnesium parvum.

Prymnesium parvum is an environmentally harmful algae and well known for its toxic effects to the fish culture. However, there is a dearth of studies on the growth behavior of P. parvum and information on how the availability of nutrients and environmental factors affect their growth rate. To address this knowledge gap, we used a uniform design approach to quantify the effects of major nutrients (N, P, Si and Fe) and environmental factors (water temperature, pH and salinity) on the biomass density of P. parvum. We also generated the growth model for P. parvum as affected by each of these nutrients and environmental factors to estimate optimum conditions of growth. Results showed that P. parvum can reach its maximum growth rate of 0.789, when the water temperature, pH and salinity is 18.11 °C, 8.39, and 1.23‰, respectively. Moreover, maximum growth rate (0.895-0.896) of P. parvum reached when the concentration of nitrogen, phosphorous, silicon and iron reach 3.41, 1.05, 0.69 and 0.53 mg/l, respectively. The order of the effects of the environmental factors impacting the biomass density of P. parvum was pH > salinity > water temperature, while the order of the effects of nutrients impacting the biomass density of P. parvum was nitrogen > phosphorous > iron > silicon. These findings may assist to implement control measures of the population of P. parvum where this harmful alga threatens aquaculture industry in the waterbodies such as Ningxia region in China.

Polysaccharides of vinegar-baked radix bupleuri promote the hepatic targeting effect of oxymatrine by regulating the protein expression of HNF4α, Mrp2, and OCT1.

ETHNOPHARMACOLOGICAL RELEVANCE: Vinegar-baked Radix Bupleuri (VBRB) is a processed form of Bupleurum chinense DC. As a well-known meridian-guiding drug, it is traditionally used as a component of traditional Chinese medicine formulations indicated for the treatment of liver diseases. However, the liver targeting component in VBRB remains unclear. Therefore, this study aims to explore the efficacy and mechanism of PSS (polysaccharides in Vinegar-baked Radix Bupleuri) in enhancing liver targeting. MATERIALS AND METHODS: Drug distribution of OM alone or combined with PSS was investigated in vivo. Relative uptake efficiency (RUE) and relative targeting efficiency (RTE) were calculated to evaluate liver targeting efficiency. The mRNA and protein expression of organic cation transporter 1 (OCT1), multi-drug resistance protein 2 (Mrp2), and hepatocyte nuclear factor 4α (HNF4α) in the liver were determined by q-PCR and Western blot. Then, AZT, the inhibitor of OCT1 and BI6015, the inhibitor of HNF4α were used to investigate regulatory mechanisms involved in the uptake of OM in the cell. At last, the role of PSS in the anti-hepatitis B virus (HBV) was explored on HepG2.2.15. RESULTS: PSS increased the AUC of OM in the liver and increase the RUE and RTE in the liver which indicated a liver targeting enhancing effect. The mRNA and protein expression of OCT1 was increased while Mrp2 and HNF4α decreased. PSS could increase the uptake of OM in HepG2 by increasing the protein expression of HNF4α and OCT1, while inhibited Mrp2. Moreover, PSS combined with OM could enhance the anti-HBV effect of OM. CONCLUSION: PSS enhanced the liver targeting efficiency and the underlying mechanism related to up-regulating the expression of OCT1 and HNF4α, while down-regulating of Mrp2. These results suggest that PSS may become a potential excipient and provide a new direction for new targeted research.

Platycodon grandiflorus enhances the effect of DDP against lung cancer by down regulating PI3K/Akt signaling pathway.

Cisplatin (DDP) is a first-line drug for non-small cell lung cancer (NSCLC), but its efficacy and applications are constrained by intolerance and serious side effects. Platycodon grandiflorus (PG) is usually used as lung medicinal drug to enhance other drug's effect on lung diseases. Therefore, present study aim to investigate anti-NSCLC effect of PG with DDP and mechanism involved in the combination for the first time. The results showed that compared with DDP group, the combined groups (DDP combined with 1, 2 and 4 g/kg of PG) reduced the tumor luminescence density by 26.0%, 78.2% and 32.8% respectively, and decreased the death rates, lung index, pathological damage and inflammation in lung tissue. Protein analysis of lung tissue showed that its anticancer effect may be associated with tumor cell apoptosis. Therefore, vitro studies showed that PG combined with DDP down-regulated the expression of p-Akt and PI3K and improved the protein expression of cleaved-caspase 9 in A549 cell and PG promotes the apoptosis of DDP and these mechanisms were related by inhibition of the PI3K/Akt signaling pathway. Our study confirms that the combination of PG and DDP will help enhance efficacy of DDP and is important for improving platinum-based chemotherapy.

Saikosaponin b2 enhances the hepatotargeting effect of anticancer drugs through inhibition of multidrug resistance-associated drug transporters.

AIMS: Vinegar-baked Radix Bupleuri (VBRB) potentiates the activity of anticancer drugs in the liver by increasing their hepatic distribution. However, this phenomenon may be associated with drug transporters. We investigated the effect of saikosaponin b2 (SSb2; the main component of VBRB) on the activity and expression of different drug transporters in both normal cells and those that overexpress the transporter. MAIN METHODS: The activities of transporters were analyzed by concentration of their cellular substrates. Concentrations of colchicine (substrate of Pgp and MRP1) and cisplatin (substrate of OCT2 and MRP2) were determined by high-performance liquid chromatography (HPLC). The concentration of rhodamine B was determined by flow cytometry. The expression of transporter gene and protein were determined by qRT-PCR and Western blotting analysis. KEY FINDINGS: SSb2 increased colchicine efflux in HEK293 cells by primarily increasing Mrp1 activity, independent of gene and protein expression. SSb2 enhanced Mrp2 function and increased cisplatin efflux in BRL3A cells by upregulating Mrp2 gene expression, with a marginal effect on Pgp in normal cells. SSb2 increased OCT2 activity in OCT2-HEK293 cells by increasing the expression of OCT2 protein and mRNA; however, SSb2 inhibited MRP2 activity in MRP2-HEK293 cells by decreasing MRP2 protein expression, and decreased Pgp and MRP1 activity in Pgp- and MRP1-HEK293 cells. SIGNIFICANCE: SSb2 might potentially be the key active component of VBRB that enhances the hepatotargeting of anticancer drugs through the inhibition of multidrug resistance-associated drug transporters (Pgp, MRP1, and MRP2) in an environment-dependent manner.

Enhanced liver-targeting via coadministration of 10-Hydroxycamptothecin polymeric micelles with vinegar baked Radix Bupleuri.

BACKGROUND: Vinegar baked Radix Bupleuri (VBRB) is a wildly used traditional Chinese medicine, it could be used as a meridian guided drug to enhance liver targeting efficiency of the delivered drug in addition to its therapeutic effect. PURPOSE: To investigate the liver targeting effect induced by VBRB via coadministration with 10-Hydroxycamptothecin loaded polymeric micelles. METHODS: First of all, the inhibitory effect of VBRB on the activity of glutathione S-transferase (GST) was investigated in vitro to select the most effective extract. After oral administration of 10-Hydroxycamptothecin (HCPT) polymeric micelles with low, medium and high doses of VBRB, pharmacokinetic parameters, including the ratio of Cmax in the liver (Ce) and the relative uptake efficiency (RUE), were employed to assess the liver targeting efficiency. RESULTS: It was found that VBRB extract BC1 has the strongest inhibition effect on GST activity in the five extracts. By coadministration of HCPT loaded micelles with three doses of BC1, the AUC0-t of HCPT in the liver raised by 42.5%, 23.0%, -0.2%, with RUE 1.45, 1.23, 1.02 for low, medium and high dose groups, respectively, indicating that low and medium dose of BC1 presented better liver-targeting enhancing effect than that of the high dose, which corresponded to the commonly used dose of VBRB in traditional Chinese medicine formulae. CONCLUSIONS: VBRB could effectively enhance the liver-targeting efficiency of HCPT loaded polymeric micelles after oral coadministration. Such a simple but effective strategy may enlighten on the potential use of meridian guided drug together with modern drug delivery system to achieve better active drug targeting.

Adjuvant Photothermal Therapy Inhibits Local Recurrences after Breast-Conserving Surgery with Little Skin Damage.

Adjuvant treatments following breast-conserving surgery (BCS) are essential to reduce the risk of local recurrences in patients with breast cancer. However, current adjuvant treatments are based on ionizing radiation, which brings radiation-induced damage and amplifies the risk of death. Here we explore the feasibility of using non-ionizing light to induce photothermal therapy as an adjuvant treatment to BCS. In an orthotopic breast cancer mice model, we demonstrate that adjuvant photothermal therapy (aPTT) decreases the incidence of local recurrences after BCS with no expense of cosmetic outcome. In comparison with conventional photothermal therapy, the technique used in aPTT provides more uniformly distributed light energy and less risk of skin burns and local recurrences. Overall, this work represents a departure from the traditional concept of using PTT as an alternative to surgery and reveals the potential of using PTT as an alternative to adjuvant radiation therapy, which is valuable especially for patients susceptible to radiation damage.

Smilax glabra Rhizoma affects the pharmacokinetics and tissue distribution of methotrexate by increasing the P­glycoprotein mRNA expression in rats after oral administration.

Methotrexate (MTX) is a widely used immunosuppressant and anticancer agent with high toxicity. Smilax glabra Rhizoma (SGR) has the effect of detoxification and immunoregulation, and has been used as both food and folk medicine in many countries. Co­administration of MTX and SGR occurs in several diseases. However, whether they work synergistically or are incompatible remains unknown. In the present study, MTX was administrated to rats alone or combined with SGR. Blood and tissue samples were collected at designated times. The concentrations of MTX were determined by high­performance liquid chromatography. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detected the gene expression. SGR decreased the AUC0­t and Cmax of MTX by 44.5 and 48.2%, but in a tissue­dependent manner. The total exposure of MTX was significantly decreased in the small intestine, stomach, plasma, and kidney by 61.6, 34.7, 63.3 and 46.1%, respectively, but was increased in the lung and spleen by 82.9 and 21.0%, respectively. RT­qPCR demonstrated that SGR increased the mean P­glycoprotein (gp) mRNA expression in the small intestine 2.54 times, but had a marginal effect on the expression of organic anion transporting polypeptide 2, and organic anion transporter (OAT)1 and OAT2. These results suggested that SGR affects the pharmacokinetics of MTX in a tissue­dependent manner by affecting P­gp, and the clinical effect of co­administration depended on the disease site.

Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is an acute and serious diabetic complication characterized by renal hypertrophy and renal fibrosis with the expansion of extracellular matrices. Diabetic nephropathy has become a major cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound prescription which has been widely applied in clinical medicine for the prevention and treatment of diabetic nephropathy as well as for acute and chronic kidney injuries. However, the mechanism of protective effects of SZGB in DN remains unclear. MATERIALS AND METHODS: In this research, we investigated the effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by performing a right uninephrectomy along with a single intraperitoneal injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D, SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage for 12 weeks. Samples from urine, blood and kidneys were collected for biochemical, histological, immunohistochemical and western blot analyses. RESULTS: We found that rats treated with SZGB showed reduced 24-h urinary protein excretion along with reduced serum total cholesterol (TC) and triglyceride (TG) levels. SZGB was also shown to prevent the disruption of catalase activity and reduce serum urea, creatinine, and renal malondialdehyde while increasing glutathione levels. Moreover, SZGB administration markedly improved the expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased the expression levels of Vimentin, α-SMA and Cleaved caspase-3 in the kidneys of diabetic rats. The renoprotective effects of SZGB was believed to be mediated by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. CONCLUSIONS: Therefore, it is suggested that SZGB can restrain epithelial-mesenchymal transition (EMT) through stimulating the Nrf2 pathway, which improves renal interstitial fibrosis in DN.

Clerosterol from vinegar-baked radix bupleuri modifies drug transport.

Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.

Telephone-adapted Mindfulness-based Stress Reduction (tMBSR) for patients awaiting kidney transplantation.

BACKGROUND: Patients with progressive kidney disease experience increasing physiologic and psychosocial stressors and declining health-related quality of life (HRQOL). METHODS: We conducted a randomized, active-controlled, open-label trial to test whether a Mindfulness-based Stress Reduction (MBSR) program delivered in a novel workshop-teleconference format would reduce symptoms and improve HRQOL in patients awaiting kidney transplantation. Sixty-three transplant candidates were randomized to one of two arms: i) telephone-adapted MBSR (tMBSR, an 8-week program of meditation and yoga); or ii) a telephone-based support group (tSupport). Participants completed self-report questionnaires at baseline, post-intervention, and after 6-months. Anxiety, measured by the State-Trait Anxiety Inventory (STAI) post-intervention served as the primary outcome. Secondary outcomes included: depression, sleep quality, pain, fatigue, and HRQOL assessed by SF-12 Physical and Mental Component Summaries (PCS, MCS). RESULTS: 55 patients (age 54±12yrs) attended their assigned program (tMBSR, n=27; tSupport, n=28). 49% of patients had elevated anxiety at baseline. Changes in anxiety were small and did not differ by treatment group post-intervention or at follow-up. However, tMBSR significantly improved mental HRQOL at follow-up: +6.2 points on the MCS - twice the minimum clinically important difference (95% CI: 1.66 to 10.8, P=0.01). A large percentage of tMBSR participants (≥90%) practiced mindfulness and reported it helpful for stress management. CONCLUSIONS: Neither mindfulness training nor a support group resulted in clinically meaningful reductions in anxiety. In contrast, finding that tMBSR was more effective than tSupport for bolstering mental HRQOL during the wait for a kidney transplant is encouraging and warrants further investigation. ClinicalTrials.govNCT01254214.

Formula PSORI-CM01 inhibits the inflammatory cytokine and chemokine release in keratinocytes via NF-κB expression.

Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced. Th1 related cytokine IFN-γ and Th17 related cytokine IL-17/IL-22 was used to induce inflammatory models on human keratinocyte cell line HaCaT in vitro, respectively. PCM01CS significantly reduced IFN-γ induced mRNA expression of IL-6, IL-12 and CXCL-10, reduced IL-6 and CXCL-10 release into HaCaT supernatant. 20ng/ml IL-17/IL-22 co-stimulation significantly upregulated expression of IL-6, IL-8 and CCL20 mRNA expression in HaCaT cells, PCM01CS significantly inhibit these cytokines expression both in mRNA and in protein levels. Finally, PCM01CS could obviously inhibit nuclear NF-κB p65 expression which activated by IFN-γ and IL-17/IL-22 stimulation. Thus, our new findings reveal that Formula PSORI-CM01 may possess therapeutic action on psoriasis by inhibiting inflammatory within skin environments.

Vinegar amount in the process affected the components of vinegar-baked Radix Bupleuri and its hepatoprotective effect.

BACKGROUND: Bupleuri Radix (in Chinese Chaihu), the dried roots of Bupleurum Chinense DC, is a traditional Chinese medicine widely used to treat fever, hepatitis, jaundice, nephritis, dizziness. When baked with vinegar, its effect is more focused on liver related disease. This paper was undertaken to determine the best vinegar amount in the processing and explore its key efficacy components. METHODS: Hepatoprotective effects of Radix Bupleuri after processing with different amount of vinegar (1:5, 2:5, 3:5) were investigated on liver hurt rats, and the change of constituents were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: With the increasing amount of vinegar, the hepatoprotective effects of vinegar-baked Radix Bupleuri (VBRB) and the content of saikosaponin b2 increased. CONCLUSION: These results suggested that vinegar amount in the process affected the pharmacological effect of VBRB significantly and saikosaponin b2 may be the key efficacy component of it.

Formula PSORI-CM01 eliminates psoriasis by inhibiting the expression of keratinocyte cyclin B2.

BACKGROUND: Psoriasis is a chronically recurrent inflammatory skin disease, modern medicine could achieve good therapeutic effect, but these treatments led to recurrence of the psoriasis, more severe symptoms due to damaging skin barrier. Traditional Chinese medicine is a useful alternative therapies. The purpose of this study was to explore the mechanism of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, in eliminating psoriasis by studying its effects on inhibiting epidermal hyperplasia. METHODS: Imiquimod induced psoriasis-form mice model was used to determine the efficacy of PSORICM-01 by assessing the improvement of hyperplasia in epidermal and dermal skin, cyclin B2 expression in skin was detected by immunochemistry. Human keratinocyte cell line HaCaT stimulated by LPS or not was used to research molecular mechanisms of PSORIMCM-01 as in vitro model. The inhibition of proliferation of HaCaT was determined by MTT assay, BrdU assay and real-time cell analysis (RTCA). Cell cycle distribution was detected by flow cytometry. Real-Time PCR and western blot analysis was performed to quantify the mRNA and protein expression levels, respectively. The ability of PSORICM-01 to inhibit proliferation of cyclin B2 overexpressed HaCaT cell were also investigated. RESULTS: PSORI-CM01 significantly inhibited epidermal hyperplasia in IMQ mice lesion skin, and reduced expression of epidermis cyclin B2. Serum containing PSORI-CM01 dramatically inhibited keratinocyte HaCaT cell proliferation, no matter stimulated by LPS or not. FACS analysis showed ability of PSORICM-01 to arrest cell cycle in the G2/M phase. Additionally, PSORI-CM01 significant downregulated mRNA and protein expression of cyclin B2, and over-expression of cyclin B2 antagonized the anti-proliferative effect of PSORI-CM01 on HaCaT cells. CONCLUSIONS: PSORI-CM01 inhibits epidermal hyperplasia in imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro. Our results indicate that PSORI-CM01 may possess therapeutic potential for psoriasis by inhibiting keratinocyte proliferation through downregulation of cyclin B2.

Two new γ-pyrone glucosides from Paeonia albiflora.

Two new γ-pyrone glucosides, along with three known compounds, were isolated from the roots of Paeonia albiflora, and their structures were elucidated by spectral experiments, chemical analysis, and comparison with literature data. The structures of the new compounds were established as 2-(hydroxymethyl)-4-oxo-4H-pyran-3-yl-6-O-α-L-rhamnopyranosyl-ß-D-glucopyranoside (1), and 2-(hydroxymethyl)-4-oxo-4H-pyran-3-yl-6-O-galloyl-ß-D-glucopyranoside (2). The inhibitory activity on the release of TNF-α of compounds 1-5 was evaluated in vitro. This is the first report of the presence of γ-pyrone glucoside in P. albiflora.