Plants have long been recognized for their therapeutic properties. For centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of maladies. By contrast, the rise of the modern pharmaceutical industry in the past century has been based on exploiting individual active compounds with precise modes of action. This surge has yielded highly effective drugs that are widely used in the clinic, including many plant natural products and analogues derived from these products, but has fallen short of delivering effective cures for complex human diseases with complicated causes, such as cancer, diabetes, autoimmune disorders and degenerative diseases. While the plant kingdom continues to serve as an important source for chemical entities supporting drug discovery, the rich traditions of herbal medicine developed by trial and error on human subjects over thousands of years contain invaluable biomedical information just waiting to be uncovered using modern scientific approaches. Here we provide an evolutionary and historical perspective on why plants are of particular significance as medicines for humans. We highlight several plant natural products that are either in the clinic or currently under active research and clinical development, with particular emphasis on their mechanisms of action. Recent efforts in developing modern multi-herb prescriptions through rigorous molecular-level investigations and standardized clinical trials are also discussed. Emerging technologies, such as genomics and synthetic biology, are enabling new ways for discovering and utilizing the medicinal properties of plants. We are entering an exciting era where the ancient wisdom distilled into the world's traditional herbal medicines can be reinterpreted and exploited through the lens of modern science.
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The Plant List (accessed 1 June 2017); http://www.theplantlist.org/
Weng, J.-K., Philippe, R. N. & Noel, J. P. The rise of chemodiversity in plants. Science 336, 1660–1677 (2012).
Hardy, K. et al. Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus. Naturwissenschaften 99, 617–626 (2012).
Lietava, J. Medicinal plants in a Middle Paleolithic grave Shanidar IV? J. Ethnopharmacol. 35, 263–266 (1992).
Aboelsoud, N. H. Herbal medicine in ancient Egypt. J. Med. Plants Res. 4, 82–86 (2010).
Yang, S. The Divine Farmer's Materia Medica: A Translation of the Shen Nong Ben Cao Jing (Blue Poppy Press, 1998).
Li, S. The Ben Cao Gang Mu: Chinese Edition (Univ. California Press, 2016).
Patridge, E., Gareiss, P., Kinch, M. S. & Hoyer, D. An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov. Today 21, 204–207 (2015).
Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P. & McPhail, A. T. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93, 2325–2327 (1971).
Neuss, N., Gorman, M., Svoboda, G. H., Maciak, G. & Beer, C. T. Vinca alkaloids. III.1 Characterization of leurosine and vincaleukoblastine, new alkaloids from Vinca Rosea Linn. J. Am. Chem. Soc. 81, 4754–4755 (1959).
Kiyohara, H., Matsumoto, T. & Yamada, H. Combination effects of herbs in a multi-herbal formula: expression of Juzen-taiho-to's immuno-modulatory activity on the intestinal immune system. eCAM 1, 83–91 (2004).
Phillipson, J. D. Phytochemistry and medicinal plants. Phytochemistry 56, 237–243 (2001).
Courtwright, D. T. Forces of Habit: Drugs and the Making of the Modern World (Harvard Univ. Press, 2001).
Manglik, A. et al. Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 485, 321–326 (2012).
Huang, W. et al. Structural insights into μ-opioid receptor activation. Nature 524, 315–321 (2015).
Vaughan, C. W., Ingram, S. L., Connor, M. A. & Christie, M. J. How opioids inhibit GABA-mediated neurotransmission. Nature 390, 611–614 (1997).
Snyder, J. P., Nettles, J. H., Cornett, B., Downing, K. H. & Nogales, E. The binding conformation of Taxol in β-tubulin: a model based on electron crystallographic density. Proc. Natl Acad. Sci. USA 98, 5312–5316 (2001).
Saville, M. W. et al. Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 346, 26–28 (1995).
Gigant, B. et al. Structural basis for the regulation of tubulin by vinblastine. Nature 435, 519–522 (2005).
Khoury, H. J. et al. Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors. Leuk. Lymphoma 56, 120–127 (2015).
Garreau de Loubresse, N. et al. Structural basis for the inhibition of the eukaryotic ribosome. Nature 513, 517–522 (2014).
Gandhi, V., Plunkett, W. & Cortes, J. E. Omacetaxine: a protein translation inhibitor for treatment of chronic myelogenous leukemia. Clin. Cancer Res. 20, 1735–1740 (2014).
Gu, Y. et al. Small-molecule induction of phospho-eIF4E sumoylation and degradation via targeting its phosphorylated serine 209 residue. Oncotarget 6, 15111–15121 (2015).
Staker, B. L. et al. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc. Natl Acad. Sci. USA 99, 15387–15392 (2002).
Ulukan, H. & Swaan, P. W. Camptothecins. Drugs 62, 2039–2057 (2002).
Damayanthi, Y. & Lown, J. W. Podophyllotoxins: current status and recent developments. Curr. Med. Chem. 5, 205–252 (1998).
Wu, C. C. et al. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 333, 459–462 (2011).
Meng, Z. P. et al. Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca2+/calmodulin-dependent protein kinase II. Mol. Cancer Ther. 12, 2067–2077 (2013).
Gu, Y. et al. CaMKII γ, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine. Blood 120, 4829–4839 (2012).
Dolma, S., Lessnick, S. L., Hahn, W. C. & Stockwell, B. R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3, 285–296 (2003).
Stickel, S. A., Gomes, N. P., Frederick, B., Raben, D. & Su, T. T. Bouvardin is a radiation modulator with a novel mechanism of action. Radiat. Res. 184, 392–403 (2015).
Zalacain, M., Zaera, E., Vazquez, D. & Jimenez, A. The mode of action of the antitumor drug bouvardin, an inhibitor of protein synthesis in eukaryotic cells. FEBS Lett. 148, 95–97 (1982).
Wink, M. Medicinal plants: a source of anti-parasitic secondary metabolites. Molecules 17, 12771–12791 (2012).
Tu, Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med. 17, 1217–1220 (2011).
Wang, J. et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat. Commun. 6, 10111 (2015).
Wu, Y. et al. Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation. Cell. Mol. Immunol. 13, 379–390 (2016).
Li, J. et al. Artemisinins target GABAA receptor signaling and impair α cell identity. Cell 168, 86–100 (2017).
Lai, H. C., Singh, N. P. & Sasaki, T. Development of artemisinin compounds for cancer treatment. Invest. New Drugs 31, 230–246 (2013).
Samochocki, M. et al. Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors. J. Pharmacol. Exp. Ther. 305, 1024–1036 (2003).
Raves, M. L. et al. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (–)-huperzine A. Nat. Struct. Biol. 4, 57–63 (1997).
Coleman, B. R. et al. [+]-Huperzine A treatment protects against N-methyl-d-aspartate-induced seizure/status epilepticus in rats. Chem. Biol. Interact. 175, 387–395 (2008).
Wang, H. et al. Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. J. Biol. Chem. 281, 21469–21479 (2006).
Leung, D. Y. et al. Effect of anti-IgE therapy in patients with peanut allergy. N. Engl. J. Med. 348, 986–993 (2003).
Srivastava, K. D. et al. The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy. J. Allergy Clin. Immunol. 115, 171–178 (2005).
Srivastava, K. D. et al. Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells. J. Allergy Clin. Immunol. 123, 443–451 (2009).
Kattan, J. D. et al. Pharmacological and immunological effects of individual herbs in the Food Allergy Herbal Formula-2 (FAHF-2) on peanut allergy. Phytother. Res. 22, 651–659 (2008).
Ehrlich, H. Food Allergies: Traditional Chinese Medicine, Western Science, and the Search for a Cure (Third Avenue Books, 2014).
Wen, M. C. et al. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J. Allergy Clin. Immunol. 116, 517–524 (2005).
Srivastava, K., Sampson, H. A., Emala, C. W. Sr & Li, X. M. The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors. Am. J. Physiol. Lung Cell Mol. Physiol. 305, 1002–1010 (2013).
Srivastava, K. D., Sampson, H. A. & Li, X. The anti-asthma chinese herbal formula ASHMI provides more persistent benefits than dexamethasone in a murine asthma model. J. Allergy Clin. Immunol. 127, AB261 (2011).
Yang, N. et al. The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction. Phytochemistry 95, 259–267 (2013).
Yang, N. et al. Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI, inhibit memory Th2 responses in vitro and in vivo. Phytother. Res. 27, 1381–1391 (2013).
Liu, C. et al. Ganoderic acid C1 isolated from the anti-asthma formula, ASHMITM suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients. Int. Immunopharmacol. 27, 224–231 (2015).
Lam, W. et al. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci. Rep. 5, 9384 (2015).
Lam, W. et al. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci. Transl. Med. 2, 45ra59 (2010).
Chan, K. et al. Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica. J. Ethnopharmacol. 140, 469–475 (2012).
Luo, D. et al. Compound Danshen dripping pill for treating early diabetic retinopathy: a randomized, double-dummy, double-blind study. eCAM 2015, 539185 (2015).
Avanzas, P. & Kaski, J. C. Pharmacological Treatment of Chronic Stable Angina Pectoris (Springer, 2015).
Tagliaferri, M. A. et al. A phase IIb trial of coix seed injection for advanced pancreatic cancer. J. Clin. Oncol. 31, e16023 (2013).
Liu, C., Hu, Y., Xu, L., Liu, C. & Liu, P. Effect of Fuzheng Huayu formula and its actions against liver fibrosis. Chi. Med. 4, 12 (2009).
Szasz, T. Psychiatry and the control of dangerousness: on the apotropaic function of the term “mental illness”. J. Med. Ethics 29, 227–230 (2003).
Liu, J., Lee, J., Salazar Hernandez, M. A., Mazitschek, R. & Ozcan, U. Treatment of obesity with celastrol. Cell 161, 999–1011 (2015).
Lee, J. et al. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat. Med. 22, 1023–1032 (2016).
Inokuma, Y. et al. X-ray analysis on the nanogram to microgram scale using porous complexes. Nature 495, 461–466 (2013).
O’Connor, S. E. Engineering of secondary metabolism. Annu. Rev. Genet. 49, 71–94 (2015).
Cook, D. et al. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat. Rev. Drug. Discov. 13, 419–431 (2014).
The authors declare no competing financial interests.
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Li, F., Weng, J. Demystifying traditional herbal medicine with modern approach. Nature Plants 3, 17109 (2017). https://doi.org/10.1038/nplants.2017.109
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