Theacrine, a Potent Antidepressant Purine Alkaloid from a Special Chinese Tea, Promotes Adult Hippocampal Neurogenesis in Stressed Mice.

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.

The association between clinical prognostic factors and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer patients: a retrospective assessment of 94 cases with EGFR mutations.

OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74.5% objective response rate (ORR) and 97.9% disease control rate (DCR) were observed for EGFR-TKIs treatment, and a higher ORR was seen in patients with 0 and 1 ECOG scores than those with 2 or greater scores (P = 0.049). The subjects had a median PFS of 11 months and a median OS of 31 months after EGFR-TKIs treatment. ECOG score and timing of targeted therapy were factors affecting PFS, and ECOG score, smoking status and brain metastasis were factors affecting OS. In addition, ECOG score was an independent prognostic factor for PFS in stage IV NSCLC patients, and the patients with EGFR 19del mutation had a longer PFS than those with exon 21 L855R mutation (P = 0.003), while ECOG score and brain metastasis were independent prognostic factors for OS. CONCLUSIONS: The results of this study demonstrate that EGFR-TKI therapy results in survival benefits for EGFR-mutant advanced NSCLC patients, regardless of gender, smoking history, pathologic type, type of EGFR mutations, brain metastasis and timing of targeted therapy. ECOG score is an independent prognostic factor for PFS, and ECOG score and brain metastasis are independent prognostic factors for OS in advanced NSCLC patients.

Differing chemical compositions of three teas may explain their different effects on acute blood pressure in spontaneously hypertensive rats.

BACKGROUND: Heavy tea consumption is suggested to be unsuitable for hypertensive people. However, the bioactive substances in different varieties of tea leaves are very different. This study compares the effects of three Chinese teas - C. sinensis, C. ptilophylla and C. assamica var. kucha - on blood pressure (BP) and heart rate in spontaneously hypertensive rats (SHRs). RESULTS: Intragastric administration of C. sinensis extract led to an acute increase in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate in SHRs. However, C. ptilophylla and C. assamica var. kucha exerted no obvious influences on SBP, DBP or heart rate. Similar to the extract of C. sinensis, intragastric administration of caffeine also led to an acute increase in BP and heart rate in SHRs. In contrast, theobromine and theacrine - purine alkaloids predominantly contained in C. ptilophylla and C. assamica var. kucha, respectively - had no pressor effects. The effect of caffeine on BP was related to the regulation of plasma epinephrine and norepinephrine levels in SHRs. CONCLUSION: The different effects of C. sinensis, C. ptilophylla and C. assamica var. kucha on BP might be explained, at least partially, by the differences in the varieties and contents of purine alkaloids.

[Study on index components and fingerprints of crude and processed Siegesbeckia Herbs].

The change of kirenol, darutigenol and darutoside in Siegesbeckia and its first to ninth processed products were studied, and the ten fingerprints were compared, which provided the experimental basis for the study of Siegesbeckia processing tech- nology. The samples were analysed by HPLC on a SunFire-C18 column (4.6 mm x 150 mm, 5 µm) with gradient elution of acetonitrile (0.1% formic acid)-water (0.1% formic acid) at a flow rate of 1.0 mL x min(-1). Column temperaturewas 30 °C and the detected wavelength was 215, 320 nm. The calibration curves of kirenol, darutigenol and darutoside were linear in the range of 2.180-26.16, 2.900-34.80, and 1.012-6.072 mg x L(-1), respectively, and the average recoveries were 96.4%, 97.2% and 96.3% wit RSD 2.2%, 1.7% and 2.4%. This method was simple, the result was stable and had good repeatability, recovery and precision. The re- sult was the basis of the chemical contents variation in the processing of Siegesbeckia Herbs and further clarifying the effect of the changing.

[Experimental research of effect of crude and processed Herba Siegesbeckiae on anti-inflammation and anti-rheumatism].

OBJECTIVE: To find out the specialities of the effect of crude and processed Herba Siegesbeckiae on anti-inflammation and anti-rheumatism. METHOD: Experiments were made on rats with swelling foot induced by carrageenin; experiments were made on mice with swelling ear induced by xylol; experiments were made on rats with chronic granuloma; experiments were made on rats with adjuvant arthritis. RESULT: Foot swelling induced by carrageenin could be diminished with crude and processed Herba Siegesbeckiae at 6.0, 2.0 g x kg(-1). The rate of inhibition of foot swelling was more than 40%, effect of the crude drug was better than that of the processed one; both of them at 6.0, 2.0 g x kg(-1) could protect rats from primary and continuous lesion of adjuvant arthritis. The effect of the processed herb was obviously better than that of the crude one in its starting minute, strength and sustaining time. CONCLUSION: The processed Herba Siegesbeckiae has obvious inhibition effect on immune inflammation. It is better than the crude Herb. Both of them have obvious inhibition effect on inflammation caused by carrageenin, with no distinct difference.