马兜铃酸 Aristolochic Acids

马兜铃属 ( Aristolochia ) 是马兜铃科下的一种草质或木质藤本稀亚灌木或小乔木。马兜铃属约有500种。

主要分布于热带和温带地区。其中囊花马兜铃 ( A. utriformis ) 等物种存在灭绝危险。

马兜铃属植物中含有因物种、植物部位、植物生长的地理位置而含量不同的马兜铃酸 ( aristolochic acid, AA )、马兜铃内酰胺 ( aristololactams )、马兜铃喹啉 ( aristoquinolines )、马兜铃精 ( aristogins ) 以及数量不等的倍半萜类等化学物质。

中医认为马兜铃属下的马兜铃 ( A. debilis)、北马兜铃 ( A. contorta ) 、木通马兜铃  ( A. manshuriensis ) 以及防己马兜铃 ( A. fangchi ) 等皆可入药，药用的不同植物部分有着不同的中文名称：
种                           入药植物器官          中药名称           
马兜铃                                 根                    青木香
马兜铃                                 叶                    天仙藤
北马兜铃                             叶                    天仙藤
马兜铃                               果实                  马兜铃
北马兜铃                           果实                  马兜铃
木通马兜铃                         茎                    关木通
防己马兜铃                         根                    广防己           

藥用

青木香

炮制 : 除去须根及泥沙，晒干。

性味 : 辛、苦，寒。

归经 : 归肝、胃经。

功效 : 平肝止痛，解毒消肿。

主治 : 用于眩晕头痛，胸腹胀痛，痈肿疔疮，蛇虫咬伤。

用法用量 : 煎服3～9g。散剂1.5～2g，开水送服。外用适量，研末敷患处。

成药：

禁忌 : 体质虚寒者慎用，胃弱者勿服。

论述 :

1、《本草纲目》：主心腹一切气，散滞气，调诸气。

2、《南州异物志》：青木香出天竺，是草根，状如甘草也。

天仙藤

炮制 :  除去杂质，切段。

性味 : 味苦，性温。

归经 : 肝、脾、肾经。

功效 : 有行气活血，通络止痛的作用。

主治 : 用于脘腹刺痛，风湿痹痛。

用法用量 : 3～6g。

禁忌 :  含马兜铃酸，可引起肾脏损害等不良反应；儿童及老年人慎用；孕妇、婴幼儿及肾功能不全者禁用。

论述 :

1、《纲目》："流气活血。治心腹痛。"

2、《本草图经》：解风劳。得麻黄则治伤寒发汗，与大黄同服堕胎气。

马兜铃

炮制 : 1、马兜铃：搓碎去筋，筛净泥土。2、蜜兜铃：取净马兜铃，加炼熟的蜂蜜与开水少许拌匀，稍闷，置锅内用文火炒至不粘手为度，取出，放凉。（每马兜铃100斤，用炼熟蜂蜜35-40斤）

性味 :  味苦微辛、性寒

归经 : 肺经

功效 : 清肺降气，主治肺气上逆、咳嗽气喘、肺热咳血等

主治 : 清肺降气，化痰止咳平喘。用于肺热喘咳，痰中带血，咯血，失音，痔瘘肿痛。

用法用量 : 内服：煎汤，3~9g；或入丸、散。

成药 : 顺气止咳化痰丸、解结丸、猴枣散、复方蛇胆川贝散

禁忌 : 虚寒咳喘及脾弱便泄者慎服。

论述 :

1、《本草经读》：马兜铃，虽云无毒，而偏寒之性，多服必令吐利不止也。

2、《开宝本草》："主肺热咳嗽，痰结喘促，血痔瘘疮。"

3、《唐本草》记载：“其根不可多服，吐痢不止”

关木通

炮制 : 洗净，略泡，润透，切薄片，晒干。

性味 : 味苦，性寒

归经 : 归心、小肠、膀胱经。

功效 : 清心火，利小便，通经下乳。

主治 : 用于口舌生疮，心烦尿赤，水肿，热淋涩痛，白带，经闭乳少，湿热痹痛。

用法用量 : 3～6g。

禁忌 : 不可多用、久服，肾功能不全及孕妇忌服。

成药：八正散、导赤散、龙胆泻肝丸

论述 :

1、《别录》：疗脾疸常欲眠，心烦哕，出音声，疗耳聋，散痈肿诸结不消，及金疮、恶疮、鼠痿、踒折、齆鼻息肉，堕胎，去三虫。

2、《药性论》：主治五淋，利小便，开关格，治人多睡，主水肿浮大，除烦热。

3、《食疗本草》：煮饮之，通妇人血气，又除寒热不通之气，消鼠痿、金疮、踒折，煮汁酿酒妙。

4、《本草拾遗》：利大小便，令人心宽下气。

广防己

炮制 : 除去杂质及粗皮，稍浸，洗净，润透，切厚片，干燥。

性味 : 味苦、辛，大寒

归经 : 归膀胱、肺经

功效 : 祛风止痛，清热利水

主治 : 用于湿热身痛、下肢水肿、小便不利、风湿痹痛。

用法用量 : 内服、煎汤4.5～9g。

禁忌 : 因含有马兜铃酸，广防己不再用作药品生产。

论述 :

1、《本草拾遗》：“如陶所注，即是木防己，用体小同。按木、汉二防己，即是根、苗为名......藤著木生，吹气通一头，如通草。”

2、《本草图经》：“防己生汉中川谷，今黔中亦有之，但汉中出者，破之文作车辐解，黄实而香......它处者青白、虚软，又有腥气，皮皱，上有丁足子，名木防己，二月、八月采，阴干用，木防己虽今不入药，而古方亦通用之。”

腎毒性

有研究认为上述中草药中所含马兜铃酸具有消炎抗菌作用并具有一定抗癌活性，但同时具有肾毒性會引起泌尿道上皮癌為每百萬核鹼基 (nucleobase base )就有150個核鹼基基因突變，馬兜鈴酸基因突變能力強度是現今已知最強的致癌物質。

由服用这类草药导致的疾病在早期被称为“中草药肾病”(Chinese herbs nephropathy，CHN)，后来改称“马兜铃酸肾病”( aristolochic acid nephropathy，AAN)。

历史

1993年，比利時發生婦女服用香港進口含防己和厚朴的減肥中藥，發生腎衰竭，引起醫學界注意。之後醫學界發表多篇論文，認為馬兜鈴酸 ( AA ) 成份可能是元兇。

2001年4月，美国食品药品监督管理局（FDA）发布了一份消费者安全警报，用以提醒使用含有AA 的“传统药方”或膳食补充剂等植物提取物产品对健康造成的危害。 AA 的产品“可能导致永久性的肾损害，并可能引发需要通过透析或肾移植方能治疗的肾衰竭”。此外，FDA还提到某些病人因服用此类产品罹患癌症，尤其是发生在尿路的癌症。台灣衛生署要求加註警語，但未禁用相關藥材。

台灣自2003年因馬兜鈴酸事件，引發中西醫論戰。11月正式禁用關木通、廣防己、青木香、天仙藤、馬兜鈴等五種含馬兜鈴酸中藥材。

因为马兜铃酸具有致突变性，国际癌症研究机构於2008年利用马兜铃属植物制作的草药列为1类致癌物，并将马兜铃酸类物质的天然混合物列入2A类致癌物。

《中国药典》2005年版起，已不再收录关木通、广防己、青木香等含有马兜铃的中药方，并使用其他品种替代。此外，对于其他含马兜铃酸生药的药用部位也进行了更改。如在2000年版以前的《中国药典》中细辛的药用部位均为“全草”，但后来考虑到细辛地上部分AA 含量较高，且古代中医一直仅使用根部，及《日本药局方》也仅用“根和根茎”，所以2005年起《中国药典》亦将药用部位修订为根和根茎。

《中国药典》2010年版进一步规定，依照高效液相色谱法测定，按干燥品计算细辛中AA I的含量不得过0.001%。

2013年，科学家发现AA 造成的基因突變位点，并证明 AA引起基因突變的能力是現今已知所有物质中最強的，在每百萬鹼基中就有150個鹼基基因会发生突變。同时也首次证明了AA 具有的肝毒性。

马兜铃酸

马兜铃酸（Aristolochic acids，简称AAs）也被称为马兜铃总酸、增噬力酸或木通甲素。这类有机化合物天然存在于诸如马兜铃属（Aristolochia）及细辛属（Asarum）等马兜铃科 ( Aristolochiaceae ) 植物中，而这些植物曾广泛地被用作中草药。此外，依靠吸食这类植物生存的蝴蝶体内也有马兜铃酸。马兜铃酸Ⅰ( AA I ) 是最常见的一种马兜铃酸类化合物，它可在几乎所有马兜铃属植物中发现，并常与马兜铃内酰胺（aristolactams）共存。

含马兜铃酸的中药材 :
中药名称         入药植物器官            种                                          
细辛                           根                      Asarum sieboldii

杜衡                           全株                  Asarum forbesii

金耳环                       全株                  Asarum pulchellum

乌金草                       全株                  Asaum longerhizomatosum

汉中防己                   根                      Aristolachia heterophylla

寻骨风                       根                      Aristolochia mollissima

淮通         根、茎              Aristolochia moupinensis        

朱砂莲                       根                      Aristolochia cinnabarina

三筒管                       根                     Aristolochia champiionii        

管南香                       根                      Aristolachia cathcartii

藤香                           根                      Aristolochia debilis

背蛇生                       根                      Aristolachia tuberosa

南木香                       根、茎及藤      Aristolochia yunnanensis

假大薯                       根                      Aristolochia tagala

蝴蝶暗消                   根                      Aristolochia transsecta

逼血雷                       根                      Aristolochiia tubiflora

白金果榄                   根                      Aristolochia versicolor

追风藤                       全株                  Hedera nepalensis         

Clinacanthus nutans: A Review of the Medicinal Uses, Pharmacology and Phytochemistry

Asian Pacific Journal of Tropical Medicine

Volume 9, Issue 4, April 2016, Pages 402–409

Authors : Ariful Alam, Sahena Ferdosh,  Kashif Ghafoor, Abdul Hakim, Abdul Shukor Juraimi, Alfi Khatib, Zaidul I. Sarker.

Clinacanthus nutans Lindau is known as snake grass, sambung nyawa, etc,  belonging to the Acanthaceae family. This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes, insects and snake bites, lesions caused by herpes simplex virus, diabetes, and gout in Malaysia, Indonesia, Thailand and China.

Phytochemical investigations documented the varied contents of bioactive compounds from this plant namely flavonoids, glycosides, glycoglycerolipids, cerebrosides and monoacylmonogalatosylglycerol.

The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory, antiviral, antioxidant, and anti-diabetic activities. The findings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.

However, further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability for future drugs. This review summarizes the medicinal uses, phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.

C. nutans (Burm. f.) Landau. (a) whole plant; (b) leaves; (c) leaves with stem.

http://dx.doi.org/10.1016/j.apjtm.2016.03.011

The Star : Alternative Treatments for Dengue Fever

Sunday April 13, 2014

BY TAN SHIOW CHIN

DENGUE fever is a problem that just does not seem to want to go away in Malaysia. And even worse, it seems to be escalating.

The latest report from the Health Ministry states that as of March 22, both the number of cases and deaths nationwide for the year have increased by 314% compared to the same period last year.

The number of dengue cases in the latest report totalled 23,633, while the number of deaths was 58.

The problem is not just limited to Malaysia, although we are considered an endemic dengue hotspot.

The World Health Organisation (WHO) estimates there may be 50-100 million dengue infections globally every year, with two-fifths of the world population, or 2.5 billion people, at risk of this mosquito-borne infectious disease.

While being infected with dengue is an unpleasant experience – it is also known as breakbone fever – with typical symptoms being fever, headache, rashes, and muscle and joint pains, a healthy person’s immune system usually has no problems fighting the virus off.

The problem comes when dengue haemorrhagic fever develops.

This extreme form of the illness causes severe bleeding due to “leaky” blood vessels and delay in blood-clotting caused by low levels of platelets, which are essential in forming blood clots.

According to the WHO, an average of about 2.5% of those who develop dengue haemorrhagic fever die.

This number can exceed 20% in cases with no proper treatment, while the risk of death in those who receive the proper supportive treatment is less than 1%.

There is no cure for dengue, nor is there any vaccine for it, although there are several research teams currently working on one.

The main method of controlling this disease is via prevention; for example, ensuring that there is no stagnant water or any container where water can pool in around, fogging, using mosquito nets and repellent, and covering up or staying indoors at dawn and dusk when the Aedes mosquitoes are most active.

Medical management of dengue is purely supportive, with maintenance of the body’s fluid balance being the key objective, whether via oral rehydration therapy, intravenous fluid replacement, or in the worst-case scenario, blood transfusion.

With no definitive treatment from modern medicine available, it is not surprising that many have turned to alternative therapies for relief.

Papaya leaf juice

This is probably the most well-known alternative treatment for dengue.

Several small scientific studies have been carried out in dengue-endemic countries like India and Malaysia, looking into the efficacy of this herbal remedy.

While the results cannot be said to be definitive, due to their small study size, they are certainly promising.

The main effect of this juice lies in raising the level of platelets in dengue patients – a critical aspect of this viral infection.

One study, conducted by the Institute for Medical Research and Hospital Tengku Ampuan Rahimah, Klang, Selangor, reported that patients given papaya leaf juice showed a significant rise in their platelet levels 40 hours after first receiving the juice, compared to patients in the control group who were only on standard supportive therapy.

The open-label randomised controlled trial, published in Evidence-Based Complementary and Alternative Medicine last year, had a total of 228 participants recruited from the hospital’s dengue ward, divided almost equally between the control group and the juice group.

The patients in the juice group took the pure fresh juice extracted from 50gm of clean papaya leaves of the sekaki variety once daily for three consecutive days.

Pharmacist and holistic medicine practitioner Datuk Dr Rajen M adds that a blend of raw young papaya and papaya leaves made into a juice, taken two to three times a day, is one of the alternative therapies for dengue in Ayurvedic medicine.

He notes that consuming papaya in general is safe, and taking it does not contradict medical advice.

Tawa-tawa

This hairy herb is commonly used in the Philippines as an alternative treatment for dengue fever.

Also known as gatas-gatas or by its scientific name Euphorbia hirta, it is said to increase the platelet levels in dengue patients.

A 2012 animal study conducted by pharmacy students from the University of Santo Tomas, Manila, showed that a decoction of tawa-tawa did indeed increase platelet levels and decrease bleeding time in rats with induced thrombocytopenia (i.e. an abnormally low platelet level).

The Philippine’s Department of Science and Technology is currently researching the effect of this plant on dengue fever, and have stated their concern over possible toxicity resulting from overdosing on tawa-tawa.

Meanwhile, Philippine Star columnist Dr Willie T Ong said in a 2009 article that Filipino doctors in general allow dengue patients to take tawa-tawa as long as they clear it with them first.

He also explained how to prepare the herb: “Take five whole tawa-tawa plants. Cut off the roots, then wash and clean.

“Boil tawa-tawa in a pot of clean water. Pour the liquid and then let cool. Sip one glass three to four times a day.”

Traditional Chinese medicine

Inti International University Center for Traditional Chinese Medicine director and head of the traditional Chinese medicine (TCM) programme Dr Yong Kian Fui says that there is no cure for dengue fever in TCM either, and treatment is usually supportive based on the stage of the disease.

The acupuncturist and Chinese physician notes that because of the vague symptoms of dengue fever, most people are only diagnosed with the disease about four days after their fever starts.

TCM therapy at that stage consists of a herbal concoction based on the formulation called qin wen bai tu san.

“This helps to clear the plaque and detox the body,” he says.

Patients have to take one dose daily for three days. If their platelet levels are still low by the end of that period, Dr Yong says they would be referred to the hospital for further management.

He adds that he personally also prescribes a bitter gourd and meat soup, which should be double-boiled for two hours.

While the meat can be from any animal, including fish, it is crucial that the seeds in the bitter gourd must be included in the soup.

“According to TCM theory, bitter gourd is used to clear ‘fire’ and to detox the body.

“The meat neutralises the bitter gourd, so that it doesn’t become too ‘cooling’.”

Ayuverdic medicine

Dr Rajen explains that there are four ways to treat dengue patients according to Ayuverdic medicine.

Two methods are targeted at boosting the patient’s blood production and providing an antiviral effect: the papaya fruit and leaf juice mix mentioned earlier, and juice made from pegaga leaves, also known as India pennywort or Centella asiatica.

According to Dr Rajen, one dose of the pegaga juice is the amount obtained from juicing one handful of leaves.

The other two treatments are mainly applied for their general antiviral properties.

One is cow or goat colostrum, which can be drunk as often as desired. Colostrum is the first secretion from the animal’s mammary glands before the milk comes out.

The other is turmeric, which can be added to the patient’s food or milk.