Design and synthesis of ligustrazine derivatives as potential anti-Alzheimer's agents.

A novel series of ligustrazine derivatives was designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitors for the treatment of Alzheimer's disease (AD). In vitro studies displayed that some of the synthesized compounds revealed promising AChE and BuChE inhibitory effects. Particularly, compounds E12 and E27, indicated highly AChE inhibitory activity with IC50 values of 1.85 µM and 0.98 µM, respectively and showed noteworthy protective effects against on glutamate-induced SH-SY5Y cells damage at 1 µM and 10 µM concentrations. Furthermore, molecular simulation docking elucidates compounds E12 and E27 interacting with residues in the binding site of AChE (PDB code: 4EY7) and BuChE (PDB code: 1P0I), emphasizing the protein residues that participate in the main interactions with the two targets. Taken together, these results revealed that compounds E12 and E27 might be potential lead compounds for further structure optimization in the drug-discovery process against AD.

[Regulation of Chrysophanol-mediated TLR4/NF-κB Pathway on Renal Injury and Immune Response in IgA Nephropathy Rats].

OBJECTIVE: To investigate the regulatory effect and its mechanism of chrysophanol (CP) on renal injury and immune response in immunoglobin A (IgA) nephropathy rats. METHODS: IgA nephropathy rat model was established by the method of lipopolysaccharide + bovine serum protein + carbon tetrachloride. Then the rats were randomly divided into 5 groups: control group, IgA group, IgA+low, medium and high dose of CP groups(2.5, 5 and 10 mg/kg for each group respectively). IgA+CP groups were intraperitoneally injected with different doses of chrysophanol once a day for 4 weeks, and the control group and IgA group were given isovolumetric saline. Urine protein content, serum creatinine and urea nitrogen were detected at 24 h after the administration of drugs. Kidney histopathological damage and apoptosis were measured by HE and TUNEL staining. The expression levels of Caspase-3 and Caspase-9 were detected by RT-PCR and Western blot; The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and (glutathione peroxidase, Gpx) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of interleukin-1ß, -6 (IL-1ß, IL-6) and tumor necrosis factor (TNF-α) in serum and kidney tissue were measured by ELISA and Western blot, respectively. The mRNA and protein expression levels of toll-like receptro 4 (TLR4), nuclear factor-κB P65 (NF-κB P65) were also detected by RT-PCR and Western blot, and vascular cell adherin molecule (VCAM-1) protein level was deteted by Western blot. RESULTS: In IgA nephropathy rats, the administration of CP reduced proteinuria, serum creatinine and urea nitrogen in a dose-dependent manner (P < 0.01). It also improved the pathological damage of kidney tissue, reduced the apoptosis rate (P < 0.01), and decreased the mRNA and protein expression levels of apoptosis-related proteins Caspase-3 and Caspase-9 (P < 0.01). CP inhibited MDA production while increased the activities of antioxidant enzymes Gpx and SOD (P < 0.01), and decreased the levels of serum and protein expression of IL-1ß, IL-6 and TNF-α (P < 0.01), as well as the expression levels of TLR4, NF-κB P65 and VCAM-1 (P < 0.01). CONCLUSION: Chrysophanol could play a protective role in IgA nephropathy rats, and its mechanism may be related to alleviating kidney injury and regulating immune response.

[Chemical constituents, biological activities and quality control of plants from genus Pyrola].

Plants from the genus Pyrola are widely distributed in North Temperate zone. The quinones, phenol glycosides, terpenoids, flavonoids and volatile oil compounds have been identified from these plants. The in vivo and in vitro studies have shown that the genus Pyrola plants exhibit a wide range of pharmacological properties, including antioxidant, antitumor, antibacterial, anti-ischemia and anti-inflammatory activities. Based on analysis of the literature of the genus Pyrola plant, this review summarized the research on chemical constituents, pharmacology and quality control in recent years which can provide evidences for further investigation on the genus Pyrola plants.

Treatment for Persistent Somatoform Pain Disorder via Electroacupuncture and a Low Dosage of Fluoxetine Hydrochloride.

CONTEXT: The clinical treatment of somatoform pain disorder (SPD) commonly combines antianxiety and antidepressant medication with pain medication, yet the method often entails a lengthy treatment, with uncertain outcomes, and, on occasion, significant side effects. Acupuncture can activate a patient's own pain control system, stimulate blood flow, repair the physical damage of emotional distress, reduce pain, lift mood, and boost the immune system. OBJECTIVE: The study intended to evaluate the benefits of adding a small dosage of fluoxetine hydrochloride (Prozac) to electroacupuncture treatment in the treatment of SPD. DESIGN: The research team performed an observational study. SETTING: The study took place at the 181st Hospital of the Chinese People's Liberation Army (Guilin, China). Participants: Participants were 64 patients who had been diagnosed with persistent SPD and who were being treated at the hospital. INTERVENTION: Participants received electroacupuncture treatment in 2 sets of points applied in 40-min sessions on alternating days, for 6 d of continuous treatment per wk, up to 8 wk. Participants were additionally treated with individualized points particular to each person's pain location. Participants also took 20 mg/d of fluoxetine hydrochloride for 8 wk. OUTCOME MEASURES: At baseline and at 1, 2, 4, and 8 wk of treatment, patients' degrees of pain, states of mind, and experiences of side effects were evaluated through the short-form McGill pain questionnaire. RESULTS: With regard to patients who had had trouble controlling chronic somatoform pain, the treatment with electroacupuncture to spots on the head, abdomen, waist, back, and sacrum, in conjunction with a light dosage of fluoxetine hydrochloride, showed reductions in pain, minimal side effects, and a low risk of relapse. CONCLUSIONS: Electroacupuncture, combined with a low dosage of fluoxetine hydrochloride, could be a beneficial treatment for chronic SPD. It avoids the risk of significant side effects from long-term ingestion of antianxiety and antidepressant medications, and the current research team has observed that it provides a relatively low likelihood of relapse. For patients with a history of untreatable persistent somatoform pain while using prescribed antianxiety and antidepression medication, the results can be rather satisfactory. It is hoped that these observations will direct further clinical research.

[Experiment research on preventive effect of matrine on rat chronic nephrotoxicity induced by cyclosporin A].

OBJECTIVE: To investigate the renal protective effect and possible mechanism of matrine on experimental cyclosporine A (CsA) induced chronic nephrotoxicity. METHODS: 56 male Sprague-Dawley rats were randomly divided into four groups: control group (olive oil 0. 2 mL/d), CsA group (CsA 20 mg/(kg x d)), Irbesartan group CCsA 20 mg/(kg x d) plus Irbesartan 10 mg/(kg x d)), matrine group CCsA 20 mg/(kg * d) plus matrine 100 mg/(kg x d)), and each group comprised fourteen rats. After treated with drugs, rats were sacrificed at the end of week 2 and 4. The body weight, 24-hours urine and blood sample were collected before rats sacrificed. The rat kidneys were taken and fixed in 10% neutral formaldehyde for HE staining. The osteopontin (OPN) and ectodermal dysplasia 1 (ED-1) were determined by immunohistochemical method. RESULTS Compared to control group, the 24-hour urine of rats, histological scores, the expression of OPN and the ED-1 positive cells number of CsA group were significantly increased, but Ccr was significantly lower (P<0. 05). Matrine could down-regulate OPN expression and decrease ED-1 positive cell infiltration in kidney, compared with CsA group (P <0. 05). CONCLUSION: Matrine has a renal protective effect on chronic cyclosporine nephrotoxicity of rat model.