Harvard scientists disclose the secrets of Chinese herbal remedy

THE SECRETS OF CHINESE HERBAL REMEDY CHANG SHAN DISCLOSED

HYDRANGEA

There in the mountains, in the north-east of the Himalayas, grows a plant, Hydrangea, commonly known as Hortensia, that may have helped scientists and researchers from Harvard School of Dental Medicine to find the answer on how to treat autoimmune disorder, an inappropriate immune response of the body against substances and molecules naturally present in our bodies [7], but mistakenly confused by our natural defenses with external pathogens, as in Lupus or psoriasis.

The researchers, lead by Malcolm Whitman, professor of developmental biology at Harvard School of Dental Medicine discovered that one of the active constituents found in the roots of Hydrangea, the halofuginone, blocked the development of Th17 cells, a type of cells present in many autoimmune disorder cases [5]. But why did their research focused on Hydrangea?


DICHROA FEBRIFUGA (HYDRANGEA)

Family: Hydrangeaceae

Genus: Hydrangea

Common name: Hortensia, Chinese: 常山, Pinyin: chángshān, Ji Gu


Hydrangea root extracts were used under the name Chang shan since more than 2000 years ago in Chinese Traditional Herbal medicine against Malaria, an illness that continues to be a global health problem affecting millions and causing the death of thousands of persons every year.

 

CHANG SHAN SELF DEFENSE MECHANISM AGAINST HERBIVORES


Plant self defense mechanism against herbivores has been developed over millenniums by some plants. Some of these mechanisms are very well developed while others are very basic. Chang shan (Hydrangea) specimens collected in the Sichuan Province of China were used to find out the self defense mechanism used by this plant, cyanogenic glucosides [16].

Cyanogenic glucosides are phytoanticipins known to be present in more than 2500 plant species. In Chang shan, as well as in other plant species, they play a very important role in its defense against herbivores.

Cyanogenic glucosides have a bitter taste and release of toxic hydrogen cyanide upon tissue disruption, something that is used by plants as a mechanism to deterr herbivore predators. Some specialized herbivores, especially insects, preferentially feed on cyanogenic plants. Such herbivores have acquired the ability to metabolize cyanogenic glucosides or to sequester them for use in their predator defense [16].

HYDRANGEA

CHANG SHAN FOR MALARIA


In the 2008 World Health Organization (WHO) report World Malaria Report, about 247 million malaria cases were reported worldwide, 87% of those cases were reported in Africa. This is mainly due to the fact that malaria parasite has been so far able to developed a certain resistance to the majority of the existing anti-malarial drugs [2], most of which are based on natural active constituents found in natural sources as artemisinin (Chinese Qinghaosu), quinine, hydroxynaphthoquinones, doxycyclin, clindamycin, and azithromycin. 

Quinine for example is a naturally occurring alkaloid extracted from the cinchona tree bark and already used by the Quechua in Peru [3].

Artemisinin was first isolated from the plant Artemisia annua, but used since ancient times in different Chinese herbal remedies [4].

Among some of these natural remedies against malaria we have to highlight another Chinese herbal remedy, named Chang Shan, a Chinese herbal remedy extracted from the root of a Hydrangea genus plant (Hortensia), an indigenous plant from Tibet and Nepal that has been in the scope of Harvard University scientists for the mechanism exerted by this herbal remedy to fight malaria.

 

HOW DOES HALOFUGINONE PREVENTS AUTOIMMUNE DISEASE?


HYDRANGEAIn spite malaria is not an autoimmune disease, the mechanism used by Hydrangea root extract (Chang shan) active constituent halofuginone, was very useful against autoimmune disease Th-17 cells.

Chang shan bioactive constituent halofuginone, a widely studied derivative of febrifugine, showed inhibitory properties against the development of T(H)17-driven autoimmunity in mouse models with multiple sclerosis [1].

It also showed certain anti-proliferative effects in acute promyelocytic leukemia in mice models [8] as well as in the prevention of cryptosporidiosis [10], a parasitic disease that has severe effects on individuals with compromised immune systems as HIV patients. It also enhanced the radiation sensitivity of human tumor cell lines [11].

Out of the several active constituents found in Chang shan (Dichroa febrifuga), Febrifugien, has been used for treating malaria-induced fever for about 2,000 years [18], the other one, Halofuginone, the halogenated derivative of febrifugine, has been tested in clinical trials for potential therapeutic applications in cancer and fibrotic disease [18].

Recently studies done on this very last active constituent, Halofuginone, reported the capacity of Halofiginone to inhibit T(H)17 (T Helper 17) cell differentiation [18]. T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17) discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease [19][20] such as multiple sclerosis (which was previously thought to be caused by Th1 cells), but also psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease [21].

As you can see a considerable number of benefits are exerted by this natural active constituent found in Hydrangea plant.

 

HYDRANGENIC ACID FROM HYDRANGEA MACROPHYLLA FOR DIABETIS


Another active constituent of Hydrangea macrophylla (Hydrangeae Dulcis Folium), hydrangenic acid, has also been found benefitial for the treatment of diabetis. In studies performed in mice, hydrangenic acid significantly lowered blood glucose, triglyceride, and free fatty acid levels after its administration to rats for 2 weeks at a dose of 200 mg/kg/day [12].

REFERENCES

[1] Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim YJ, Lee HK, Cortese JF, Wirth DF, Dignam JD, Rao A, Yeo CY, Mazitschek R, Whitman M. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
[2] How can natural products serve as a viable source of lead compounds for the development of new/novel antimalarials? Eric Guantai1 and Kelly Chibalecorresponding author1,2 1Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa 2Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, 7701, South Africa (Open access article under Creative Commons Attribution License).
[3] Wikipedia, Quinine via (http://en.wikipedia.org/wiki/Quinine#History)
[4] Wikipedia, Artemisinin via (http://en.wikipedia.org/wiki/Artemisinin)
[5] News from Harvard Medical, Dental and Publich Health Schools.
[6] Itokawa H, Morris-Natschke SL, Akiyama T, Lee K-H. Plant-derived natural product research aimed at new drug discovery. J Nat Med. 2008;62:263–280. doi: 10.1007/s11418-008-0246-z.
[7] Wikipedia Autoimmune disease.
[8] Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.de Figueiredo-Pontes LL, Assis PA, Santana-Lemos BA, Jácomo RH, Lima AS, Garcia AB, Thomé CH, Araújo AG, Panepucci RA, Zago MA, Nagler A, Falcão RP, Rego EM. Hematology Division of the Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
[10] Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in dairy calves. Trotz-Williams LA, Jarvie BD, Peregrine AS, Duffield TF, Leslie KE. Ontario Veterinary College, University of Guelph, Ontario, Canada.
[11] Halofuginone enhances the radiation sensitivity of human tumor cell lines. Cook JA, Choudhuri R, Degraff W, Gamson J, Mitchell JB. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1002, USA.
[12] Hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of antidiabetic compound. Zhang H, Matsuda H, Yamashita C, Nakamura S, Yoshikawa M. Kyoto Pharmaceutical University, Misasagi, Kyoto, Japan.
[13] A potent antimalarial activity of Hydrangea macrophylla var. Otaksa leaf extract against Plasmodium yoelii 17XL in mice. Ishih A, Ikeya C, Yanoh M, Takezoe H, Miyase T, Terada M. Department of Parasitology, Hamamatsu University School of Medicine, 3600 Handa-cho, 431-3192, Hamamatsu, Japan.
[14] Anti-inflammatory effects of aqueous extract from Dichroa febrifuga root in rat liver. Choi BT, Lee JH, Ko WS, Kim YH, Choi YH, Kang HS, Kim HD. Department of Oriental Medicine, College of Oriental Medicine, Research Institute of Oriental Medicine, Dong-Eui University, Busan 614-052, Korea.
[15] Cyanogenic glucosides and plant-insect interactions. Zagrobelny M, Bak S, Rasmussen AV, Jørgensen B, Naumann CM, Lindberg Møller B. Department of Plant Biology and Center of Molecular Plant Physiology (PlaCe), Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, DK-1871 Frederiksberg C, Copenhagen, Denmark.
[16] Two New Cyanogenic Glucosides from the Leaves of Hydrangea macrophylla. Yang CJ, Wang ZB, Zhu DL, Yu Y, Lei YT, Liu Y. College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
[17] Treatment of psoriasis vulgaris by oral administration of yin xie ping granules--a clinical report of 60 cases. Shan C, Yuan L, Xiuzhen B, Aiju Q. Beijing Moshikou Hospital of Traditional Chinese Medicine, Beijing 100041, China.
[18] ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Zhou H, Sun L, Yang XL, Schimmel P. The Skaggs Institute for Chemical Biology, Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
[19] Harrington LE, Hatton RD, Mangan PR et al. (November 2005). "Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages". Nature Immunology 6 (11): 1123–1132.
[20] Stockinger B, Veldhoen M (June 2007). "Differentiation and function of Th17 T cells". Current Opinion in Immunology 19 (3): 281–286.
[21] Wikipedia article on T-Helper 17 cells under the Creative Commons Attribution-ShareAlike License