从治疗原发性痛经新用途的发现探讨经方葛根汤现代研究的新思路

许多中医经典方（以下简称＂经方＂）至今仍具有较高的临床实用价值,关于其现代研究也具有较深远的科研示范价值。风寒感冒的代表方葛根汤,治疗寒湿凝滞型原发性痛经具有单次给药有效,连续给药不易复发的特点,不仅符合异病同治和标本兼治的中医治疗法则,在原发性痛经的治疗中也具有独特的临床优势。该文以葛根汤治疗原发性痛经新用途的发现为切入点,在课题组前期研究的基础上,提出借鉴现代医学以及生物学研究方法与成果,发掘中医药自身的理论与临床优势,充分体现葛根汤以基方为核心的经方配伍特点,遵循以生物活性为导向的化学研究思路,准确、有效地识别葛根汤治疗原发性痛经的主要活性成分（群）并阐明其可能的作用机制,最终将其开发成为药效物质明确、作用原理基本清楚的现代组分配伍中药的研究设想。该研究设想体现了在现代研究中遵循中医药自身特色与优势的必要性以及以临床疗效为核心开展基础研究的重要性,以期为经方的现代研究提供研究思路与方法借鉴。

Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea(PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction(GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F_2 alpha(PGF_(2α)) and Ca^(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF_(2α) and Ca^(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

Sheng-Mai-San attenuates contractile dysfunction and structural damage induced by chronic intermittent hypoxia in mice

Sheng-Mai-San(SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia(CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days(nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle(LV) dysfunction and structure abnormalities. After administration of SMS(0.55, 1.1, and 5.5 g·kg-1·d-1) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors(Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.

Anti-inflammatory effects of Abelmoschus manihot(L.)Medik.on LPS-induced cystitis in mice:potential candidate for cystitis treatment based on classic use

Abelmoschus manihot(L.)Medik.(A.manihot)is a traditional Chinese herbal medicine with a variety of pharmacological properties.It was first recorded in Jiayou Materia Medica dating back to the Song dynasty to eliminate urinary tract irritation by clearing away heat and diuretic effect.However,its pharmacological action on urinary tract infections has not been investigated.The present study aims to evaluate the anti-inflammatory activity of A.manihot on a mouse model of lipopolysaccharide(LPS)-induced cystitis.The results showed that A.manihot decreased white blood cell(WBC)count in urine sediments of the cystitis mice,alleviated bladder congestion,edema,as well as histopathological damage,reduced the expression levels of tumor necrosis factor-α,interleukin-6,and interleukin-1βsimultaneously.Moreover,A.manihot administration significantly downregulated the expression levels of TLR4,MYD88,IκBα,p-IκBα,NF-κB p65,and p-NF-κB p65 in LPS-induced cystitis mice.These findings demonstrated the protective effect of A.manihot against LPS-induced cystitis,which is attributed to its anti-inflammatory profile by suppressing TLR4/MYD88/NF-κB pathways.Our results suggest that A.manihot could be a potential candidate for cystitis treatment.