Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT1A receptor: Insights from transcriptomics.

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.

Therapeutic effects of topical 5-aminolevulinic acid photodynamic therapy.

OBJECTIVE: To evaluate the therapeutic effects of combined 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) on genital warts and the safety. METHODS: One hundred ten patients with genital warts who were treated in our hospital from June 2013 to October 2014 were selected. The warts and affected parts were disinfected with benzalkonium bromide solution, and the warts were covered with absorbent cotton that had already been added freshly prepared 20% ALA solution, packaged and fixed. Then they were wet-dressed in dark, into which ALA solution was added according to the proportion of 5:3:2 every 30 minutes for three consecutive hours. Afterwards, the warts were illuminated by using photodynamic laser apparatus. The clinical outcomes, adverse reactions and recurrence rates were observed. RESULTS: Genital warts were relieved in 107 out of the 110 cases (cure rate: 97.3%). Male patients had significantly better treatment outcomes at the urethral orifice than those in other affected parts. In the 107 patients, the cure rate of male patients was 98.8%, and they were cured after being treated four times. In contrast, female patients, who were cured after 5 times of treatment, had the cure rate of 91.7%. Their cure rates were similar (χ(2)=0, P>0.05), but the males were cured after significantly fewer times of treatment than the females (t=-7.432, P<0.05). Five patients suffered from mild tingling or burning sensation upon dressing at the urethral orifice, and the others were all free from systemic adverse reactions. After illumination, a small portion of the patients had mildly red, swelling, painful affected parts, with mild edema that almost disappeared within three days. Three patients relapsed at the urethral orifice and were then cured after further treatment. CONCLUSION: ALA-PDT can treat genital warts safely with high cure rate and low recurrence rate, particularly working for those of males at the urethral orifice.

Study on the therapeutic mechanisms of pseudolaric acid in mice with allergic contact dermatitis.

OBJECTIVE: To study the therapeutic mechanisms of pseudolaric acid on allergic contact dermatitis in mice. METHODS: A total of 50 BALB/C mice were selected and randomly divided into control group, model group, and treatment A, B, C groups with 10 rats in each group. ACD model was established in model group, and treatment A, B, C groups but not in control group. Model group received no treatment, but treatment A, B, C groups were treated with external application of the concentration of 0.1%, 0.2% and 0.4% of the pseudolaric acid for the lesions of ear skin. And the weight gain and the swelling degree of the mice' ear were recorded, weight of thymus and spleen were measured. Spleen suspension was prepared to test T lymphocyte and B lymphocyte levels of mice in five groups. Changes in serum IFN-γ, IL-4 and IL-10 levels were tested through the enzyme linked immunosorbent assay (ELISA). RESULTS: The weight gain of mice in model group were significant lower than those of mice in the control group and the treatment A, B, C groups (P < 0.05). Weight gain of mice in treatment A, B groups were significant lower than that of control group (P < 0.05), but the difference in weight gain between treatment C group and control group showed no significant difference (P > 0.05). The swelling degree and the weight of mice ears in model group were significant higher than those of mice in control group and treatment A, B, C groups (P < 0.05). Swelling degree and the weight of mice ears of treatment A, B, C groups were obviously higher than that of control group (P < 0.05). The swelling degree and weight of mice' ears in treatment A, B, C groups were decreased with the increase of the drug dosage, but comparison between A, B and C group showed statistically differences (P < 0.05). The thymus and spleen index of mice in model group were significant higher than those of the other four groups (P < 0.05), among the four groups, thymus and spleen index of treatment A and B group were higher than control group and treatment C group (P < 0.05). The stimulation index of T and B cells of mice in model group was significantly higher than the rest four groups (P < 0.05). The serum IFN-γ level of mice in control group and treatment A, B and C group was obviously lower than that of mice in model group (P < 0.05). The serum IFN-γ level of mice in treatment A, B and C group were decreased with the increasing of the drug dosage, and the level of C group was obviously lower than that of A and B group (P < 0.05). CONCLUSION: The pseudolaric acid has anti-inflammation and immune adjustment the effects showing a remarkable therapeutic effects for the ACD mice.

Effects of caldesmon, calponin, and tropomyosin on the Mg2+-ATPase activities of smooth muscle myosin.

OBJECTIVE: To test whether in the absence of actin, actin-binding proteins such as caldesmon, calponin, and tropomyosin interact with the myosin of unphosphorylation, Ca2+-dependent phosphorylation (CDP), and Ca2+-independent phosphorylation (CIP) and stimulate myosin Mg2+-ATPase activities. METHODS: Mg2+-ATPase activities were measured to evaluate the effects of caldesmon, calponin, and tropomyosin on the myosin in unphosphorylation, CDP by myosin light chain kinase (MLCK), and CIP by MLCK. RESULTS: (1) At different incubation-time, i.e., 5, 10, 20, 40, and 60 minutes, the highest Mg2+-ATPase activity was observed when myosin was in the state of CDP, the medium was CIP of myosin, and the lowest was the unphosphorylated myosin. (2) In the absence of caldesmon, calponin, and tropomyosin, the Mg2+-ATPase activities from high to low were in the following order: CDP, CIP, and unphosphorylated myosin. However, in the presence of caldesmon, calponin, and tropomyosin, the order of relative value of Mg2+-ATPase activities from high to low was unphosphorylated, CIP, and CDP of myosin respectively compared to the corresponding controls. CONCLUSIONS: The results propose that caldesmon, calponin, and tropomyosin are capable of stimulating Mg2+-ATPase activity of smooth muscle myosin in Ca2+-independent manner, since Ca2+ is not obligating for the stimulating effects of the three proteins. The common characteristic of the three proteins is that when myosin activities are low, their activations are relatively strong and this property might be involved in smooth muscle tension keeping.