Ethnopharmacology: Unlocking the Therapeutic Potential of Plants
Dr. Chintada Archana
Assistant Professor of Veterinary Pharmacology and Toxicology, School of Veterinary and Animal Sciences,Centurion University, Paralakhemundi, Odisha, 761 211
Using plants and plant derived pure compounds for therapeutic purposes has proven its efficacy over centuries. Many modern drug classes have roots in natural product prototypes, highlighting the enduring value of traditional remedies. Notable examples include aspirin, digoxin, ephedrine, morphine, tubocurarine, reserpine, and quinine, initially discovered through the exploration of traditional medicine and indigenous knowledge.
There is a renewed global interest in herbal products, and conventional medicine is increasingly acknowledging their use once validated through scientific research. Botanicals such as ispaghula, garlic, ginseng, ginger, ginkgo, St. John’s Wort, and saw palmetto are gaining traction among contemporary healthcare practitioners. This trend is expected to persist, partly due to the significant costs associated with developing patentable synthetic drugs.
- Historical aspects
Historians worldwide have provided substantial evidence demonstrating that nearly all early civilizations utilized plants in a highly advanced manner. For example, quinine originated from Cinchona bark was used medically to alleviate malaria symptoms long before the disease itself was understood. Similarly, the natural ingredients found in what we now recognize as aspirin were widely used as pain relievers long before the advent of tablet production technology.
By the mid-19th century, approximately 80% of all medicines were sourced from plants. However, the emergence of the pharmaceutical industry and the development of synthetic drugs marked a significant shift in medicine. Despite this, herbal remedies have remained consistently relevant. Even today, about 25% of the drugs available in Western pharmacies are plant-based. Moreover, many pharmacological drug classes continue to be inspired by natural product prototypes.
Morphine, extracted from the opium poppy (Papaver somniferum), stands as one of the earliest molecules integrated into conventional medicine and remains one of humanity’s most effective painkillers. Another iconic example is digitalis, a cardiac glycoside derived from the foxglove plant (Digitalis purpurea), which belongs to a widely used class of clinically effective compounds. These compounds are renowned for their positive inotropic effects on heart failure and their therapeutic significance.
A pivotal discovery in cardiovascular pharmacology occurred over five decades ago with the isolation of reserpine. This compound, extracted from the roots of the Indian plant Rauwolfia serpentina, was introduced to modern Western medicine in 1949 by Vakil, who documented its application in treating hypertension. Between 1952 and 1958, reserpine’s isolation, structural characterization, and total synthesis were achieved in rapid succession.
Aspirin, the acetyl derivative of salicylic acid (the active compound from willow bark), is one of the most widely used agents for its analgesic, antipyretic, and anti-inflammatory properties. Additionally, modern antithrombotic drugs owe their origins to veterinary observations in Canada during the 1920s. It was noted that cattle consuming mouldy hay made from sweet clover (Melilotus officinalis) suffered from stomach hemorrhages. Freshly cut hay contains coumarins, aromatic compounds that exhibit anticoagulant activity. This led to the synthesis of dicoumarol, a breakthrough drug still used today in the management of atrial fibrillation.
- Revival of interest in phytomedicine
Although public interest in phytomedicine has grown significantly, only a handful of drugs derived from higher plants have gained substantial recognition in conventional medical practice over the past few decades. One of the most prominent examples is Taxol, a diterpenoid initially extracted from the bark of the Pacific yew tree (Taxus brevifolia Nutt.).
There is compelling evidence of a global resurgence in the interest in phytomedicine, with this revival reaching such remarkable levels that the global sales of herbal products now exceed $100 billion annually. The East has long been recognized for its reliance on herbal medicine, with China and India leading the way in this field.
In the Western world, the popularity of phytomedicine is also growing rapidly. Within Europe, Germany stands as the leading country in the use of botanicals, followed closely by France. Approximately 80% of German physicians regularly prescribe herbal remedies, with St. John’s Wort being commonly recommended for mild to moderate depression. Similarly, Ginkgo remains a highly sought-after botanical in Europe. Notably, Germany’s healthcare system covers the cost of around 40% of the herbal remedies prescribed by its physicians. In the United States, a major Center for Complementary and Alternative Medicine has been established at the NIH with substantial funding. More recently, the NIH has taken an active role in supporting large-scale clinical trials on botanicals, including St. John’s Wort and Ginkgo.
It is a well-established fact that plants grown in different climatic conditions may exhibit variations in the chemical composition of their active compounds. Consequently, it is not surprising that the traditional uses of a plant can differ across geographical regions. For instance, Caesalpinia bonduc is used in Africa as a uterine stimulant, with this effect being attributed to its cholinergic properties. Additionally, the plant has been used as an antidiarrheal, where its effects were found to be primarily due to antispasmodic constituents acting through calcium channel blockade, along with a minor cholinergic component. In contrast, in South Asia, this plant is predominantly employed for its antispasmodic properties.
- Synergistic and/or side-effects nullifying combinations in plants
The idea of synergistic and/or side-effect-neutralizing combinations in medicinal plants is an ancient concept, first proposed by Hippocrates and later reinforced by Ibn Sina and other scholars. However, this concept remained largely unexplored and lacked sufficient scientific backing, primarily due to the limited number of ethnopharmacologists with a broad range of expertise. Our research group is actively investigating a variety of biological assays, with a particular focus on examining the significance of such combinations in plants. Interestingly, we have identified several intriguing combinations, notably the co-existence of acetylcholine (Ach) and calcium channel blocker (CCB)-like activities, which are commonly found together in many of the plants we have studied.
Building on our pioneering research into muscarinic receptor subtypes, we successfully identified the plant-derived compound himabicine as a prototype for cardio-selective antimuscarinic drugs. Later, another plant-derived drug, ebeinone, was reported. However, there remains a scarcity of selective agonists for acetylcholine receptors, which limits the therapeutic applications of cholinergic drugs.
An alternative approach to achieving a cholinergic effect is by inhibiting an endogenous enzyme, acetylcholinesterase (ACE), which is responsible for the breakdown of acetylcholine (Ach). This inhibition increases the availability of Ach at the desired site, as seen in the use of ACE inhibitors for conditions such as myasthenia gravis, senile dementia, and Alzheimer’s disease (AD). We have made progress in identifying ACE-inhibitory substances in medicinal plants.
Interestingly, medicinal plants such as Sesamum indicum, Lavandula stoechas, ginger, and Carum copticum, which have been traditionally used to lower blood pressure (BP), were found to exert this effect through a combination of calcium channel blocker (CCB) and acetylcholine (Ach)-like activities. Both CCBs and cholinergic drugs are known to produce similar inhibitory effects on the cardiovascular system, while they have opposing effects (Ach being excitatory and CCBs inhibitory) on other systems, such as the respiratory, gastrointestinal, and renal systems. This unique combination of activities may provide valuable insights for designing experiments to evaluate the clinical potential of existing drugs in these categories.
Turmeric (the rhizome of Curcuma longa) has been traditionally used as an antispasmodic and bronchodilator, among its various other uses. To provide scientific evidence supporting these uses, we demonstrated that turmeric exerts these effects through its calcium channel blocker (CCB) and phosphodiesterase (PDE) inhibitory activities.
These examples highlight the fascinating combination of effects found in plants in their natural form, demonstrating the great potential of medicinal plants as sources of new drugs used in both developing and industrialized countries. Ethnopharmacology has already contributed significantly to the development of conventional medicine and is expected to play an even greater role in the future. Collaboration among ethnobotanists, ethnopharmacologists, physicians, and phytochemists is crucial for advancing medicinal plant research.
