Research Article - Biomedical Research (2018) Volume 29, Issue 16
Accepted on September 4, 2018
Herbal medicines have recently been used for treatment of various diseases. The unwanted reaction and other concern like authenticity of herbal drugs is one of the important issues that have been addressed in this article. Toxicity of various important herbal drugs which are used regularly may also induce fatal reaction in our body. Herbal drug interaction with conventional drug and their serious consequences may be also life threatening for the patients who consume herbal drugs. Drug mutagenicity and contamination of herbal drugs are discussed here with suitable example. Drug authenticity with suitable illustration is also depicted in this review article. The aim of this article is to deliver an insight to the critical points of modern herbal drugs therapy and to find the scope for future scientists to overcome the serious issues regarding the herbal drugs treatment in recent era.
Herbal drugs, Toxicity, Drug authenticity, Drug interaction.
The herbal therapy as mainline treatment becomes very popular among the huge percentage of population in America . In addition, the government of UK in recent year spends £40 million for herbal treatment . Due to its high efficacy against mild to life threatening disease, herb drugs have acquired a huge popularity among various populations throughout the world. The uses of herbal drugs are still very limited due to its enormous side effects. The side effects and adverse reaction of the herbal drugs are mainly manifested in various forms like allergic reaction, vomiting, itching, abdominal discomfort, etc. There are several herb medicines which have various narcotic derivatives that may cause various types of drug dependency as well as permanent damaging of central nervous system. In addition drug interaction for different category of herbal drugs may endanger the patients’ health condition. For these reasons the World Health Organization (WHO) released several guidelines for agricultural plantation and collection procedure for medicinal herbs [3-9]. The main problem with medicinal plants is the quality of the raw form of the herbal medicine and the selection of wrong species. Another problem of herbal drug is its cross contamination. Contamination of parent herbal drugs may happen intentionally. Accidental contamination is also possible which may cause serious consequences. The herbal drugs may have high concentration toxic metal including arsenic, mercury, cadmium. These metals may enter into the human body with various forms of herbal drugs and have serious deleterious effects in long term uses of those herbal drugs. The use of pesticides for cultivation of medicinal plant also may cause serious effects on vital organs and also may cause carcinogenicity for long term uses for treatment of various diseases. Microbial growth including fungus formation also may be responsible for serious adverse reaction of the herbal drugs. To encounter these problems acute and subchronic toxicity can be effectively implemented to evaluate any range of toxicity which may be evolved due to use of the herbal drugs [10,11]. In this review article we will discuss various aspects of serious toxicity of herbal drugs and how to encounter these problems.
|Name of herbal drugs||Uses||Toxicity|
|Aconite||The drug is mainly used for anti-inflammatory and analgesic activity. In addition it is used for Rheumatic arthritis and cardiac disorders||Very fast-acting poison that causes severe side effects such as nausea, vomiting, weakness or inability to move, sweating, breathing problems, heart problems, and death.|
|Alfalfa||It is very much popular drug used in homeopathic medicine. It contains lots of ion including sodium, potassium, etc.||Auto immune disorder of Systemic Lupus Erythematosus (SLE) like syndrome may be induced in individuals.|
|Aloe vera||Mainly used as nutritional drink for internal consumption. Minor cuts and bruises can be treated by using Aloe vera ointment or topical formulation||Long term uses may cause depletion of potassium in human body. It may interact with glycoside and may cause life threatening electrolyte imbalance.|
|Comferey||It is used for treatments of cuts, infection and bruises. Comfrey herbal tea is good for the treatment of knit bones.||The pyrozolidine chemicals present in comferey are highly hepatotoxic. This may induce the risk of cancer.|
|Ephedra||The drug is highly effective for the treatment of respiratory diseases. The drug is also used for obesity treatment and for mood elevation.|
|The ephedra is responsible for serious side effects including restlessness and hypertension. Long term uses of ephedra may damage liver and heart permanently.|
|Ginkgo biloba||Mainly used for improvement of mental alertness and memory power.||Long term use can body hemorrhage and reduce platelet activating factor.|
|Ginseng||It is used for improvement of general immunity. It works as stress remover and antihypertensive agents.||Long term use may cause problem related with blood clotting|
Table 1. Toxicological aspect of common herbal drugs used for treatments of various ailments.
To counter all these toxicity effects, proper counseling of the patients with herbal drug physician and experts should be done. Pharmacovigilance of herbal drugs may play an important role to encounter these types of incidents.
Herbal drug interaction
Herbal drugs may interact with conventional drug and may produce some unwanted reaction in human body system. Herbal drug interaction is more dangerous than conventional drug due to presence of enormous pharmacological active constituents in single herbal medicine . Although most of the herbal drugs do not have any problems related to drug interaction, if interaction happens it results in serious consequences. Herbal drug interaction is generally moderate in nature . Due to very narrow therapeutic ranges several lifesaving drugs like ticlopidine, insulin, warfarin, digoxin, and aspirin frequently interact with some herbal drugs .
Herbal drug researchers are trying to find the exact reasons behind this interaction. Till now the exact reasons for these drug interactions were not fully understood. But some scientists have investigated that the reason behind interaction between anticancer drugs and herbal medicine is due to activity of metabolic enzyme CYP3A4 and P-glycoprotein . The interaction of various drugs is presented as follows (Table 2).
|Name of drug||Uses||Drug interaction|
|St. John's wort||Hemorrhoids, stomach upset anxiety, insomnia, mild to moderate depression fluid retention||St. John's wort induces clearance of SSRI. Cyclosporine, fluoxetine, digoxin, indinavir, and phenprocoumon, irinotecanand, imatinib type anticancer drug also interact with St. John's wort|
|Ginkgo biloba||Memory problems, Alzheimer’s disease||Exacerbate bleeding in combination with warfarin and aspirin|
|Salvia miltiorrhiza||Coronary heart diseases, cerebrovascular disorders||Bleeding may be induced in combination with warfarin|
|Allium sativum||Atherosclerosis and high blood pressure (hypertension)||Plasma concentration may be increased when combined with saquinavir, hypoglycemia may be triggered when chlorpropamide is administered along with Allium sativum|
|Ephedra||Asthma, bronchitis, hay fever, cold and flu, nasal congestion, cough||Combined with caffeine it may cause life threatening conditions|
|Black Cohosh||Vaginitis, menopausal disorders (“hot flashes”), uterine spasms and painful menstruation||Black Cohosh may induce hepatotoxicity with the following drugs: atorvastatin, acetaminophen and alcohol|
|Coenzyme Q10||Natural immune booster||Use with warfarin may cause blood clotting|
|Cranberry||Supplement of vitamin C||Cranberry may increase effect on anticoagulants|
|Echinacea||Improve immune system against cold||Echinacea reduce metabolism of caffeine|
|Ginger||Herbal supplement||Ginger induces interaction with anticoagulants like warfarin, aspirin, or other anticoagulants|
Table 2. List of various herbal drugs interact with conventional drugs.
Herbal drugs may interact with conventional drug and may produce allergic reactions. There are many herbal drugs which may produce serious allergic reaction including anaphylactic shock. In addition to anaphylactic shock it may produce itching, pruritus and rashes of skin. Asteraceae family is responsible for various types of serious allergic dermatitis [21-23].
Sunflower is very much familiar to induce contact allergy among florists and gardeners. Aroma oil and various type of volatile oil present in the cosmetics may trigger allergic reaction. The herbal plants belonging to Narcissus family which contains calcium oxalate are highly responsible for serious skin diseases like fissures and dryness, scaling erythematous dermatitis, etc. Existing skin disorders also may be exacerbated due to the contact of calcium oxalate. In addition, the flowers belonging to Asparagaceae family also induced dermatitis skin irritation. Although Aloe vera may cause skin irritation due to allergic reaction it is very rare. Garlic (Allium sativum), onion (Allium cepa) is more frequently used in herbal medicine which also induces skin irritation. Pineapple (Ananas comosus) is included in this family. It contains calcium oxalate crystals and bromelain, a proteolytic enzyme whose action is facilitated by the crystals. It is known that pineapple can cause irritations in the mouth (stomatitis, particularly angular cheilitis and perioral dermatitis). Tea tree oil-widely used as a topical disinfectant or camomile can cause allergic reactions.
Herbal drugs may have the potential to change the genetic code of DNA. The common herbal drugs used for the treatment of various ailments have shown some serious mutagenicity . Table 3 depicts toxicity of various plants which shows mutagenicity. Herbal drug interaction is more dangerous compared to conventional drugs due to presence of enormous pharmacological active constituents in single herbal medicine .
|Name of herbal drugs||Uses||Mutagenic reaction|
|Anthranoid such as aloe, cascara, rhubarb and senna.||Used for laxative purpose||Use of anthranoid laxatives are highly associated colorectal carcinoma|
|Chaparrel||Used for tea||Cystic renal cell carcinoma may develop after regular uses of Chaparrel tea|
|Vinca leafs||Used for treatment of various cancerous diseases||Vincristine (VCR), Vinblastine (VBL) and Vinorelbine (VRL) are anticancer agents which may induce genotoxicity|
Table 3. Mutagenicity of various herbal plants.
Although most of the herbal drugs do not have any problems related to drug interaction, it may result in serious consequences if there’s any interaction. Herbal drug interaction is generally moderate in nature . Due to very narrow therapeutic range several lifesaving drugs like ticlopidine, insulin, warfarin, digoxin, and aspirin frequently interact with some herbal drugs [26,27]. Herbal drug researchers are trying to find the exact reasons behind this interaction. Till now it was not fully understood the exact reason for these drug-drug interaction. But some scientists have explored that the reason behind interaction between anticancer drugs and herbal medicine is due to activity of metabolic enzyme CYP3A4 and P-glycoprotein . The interaction of various drug interactions is presented here.
One of the biggest problems with herbal drugs is contamination or adulteration. Compared to conventional drugs herbal medicine evaluation of quality control parameter is less stringent. Most of the herbal drugs originated from Asia contain heavy metals like lead, arsenic, mercury, etc. In 1989, a contaminated batch of L-tryptophan herbal drugs was responsible for outbreak of life threatening disease eosinophilia-myalgia syndrome. Another type of contamination is possible in the form of microbial contamination. The improper transportation and humid condition is mainly responsible for fungal infection of herbal drugs. The unscientific method of cultivation and collection of raw herbal drugs also may be one of the salient reasons for pathogenic contamination. Sometimes herbal drugs are contaminated due to exposure of human pathogenic organism .
False authentication and identification is a serious issue which may cause fatal consequences for the patients who consume herbal drugs. The false authentication may be due to several reasons, although very of them are may be done deliberately. One of the most common examples of false authentication is ginseng preparation. To identify the difference between false and real drug human expertise is needed to evaluate the morphological structure of the drug. In few cases expert taxonomists are also unable to identify the true herbal drugs. Modern analytical techniques like HPLC, FT-IR and LC-MS can be used successfully to identify the chemical structure of the drugs [29-31]. Yet these techniques are not very accurate and effective to find the adulterant if it is mixed in minute quantity. For this reason it is highly required to find some simple and economic method to evaluate the authentication of the herbal drugs [32-36].
In ancient civilization, people used to find the remedies form the natural resources-plants, herbs, as there was no trace of modern medicines. Even now, among the tribal community, we can find a wide range of natural remedies to treat the health problems or diseases. With the historical experiences which were accumulated over thousands of years, we are now shaping these with a scientific approach. A lot of research and developments are conducted to establish the evidence for the herbal medicines [33-49].
The main issue of a medicine is its effectiveness as well as its safety. Drug toxicity and side effects have recently become a major issue in public health. We can experience the realization gained though the safety monitoring (i.e. pharmacovigilance) in case of modern medicine [34,35]. Herbal drugs although being somehow less toxic and having less serious side effects, it cannot be excluded fully from toxic drugs. Several photochemicals are recently used in pharmaceutical industry for the treatment of various diseases. In addition herbal drugs are also used as nutrient and immune boosters. In previous review and research article many authors have explained in detail various safety issues of herbal drugs. Most of the studies mainly concentrated on side effects of various drugs used as herbal preparation. Very few researchers have pointed out the issue of authentification and contamination [37,38].
The herbal drugs are lacking far behind in proper safety monitoring, adverse event reporting system, etc. Though the regulation and specification of herbal medicines are different country-wise, the need of pharmacovigilance is essential to promote the safe use of herbal medicines. Therefore attempts were made in this review article to address all the challenges of herbal drugs in the recent era in terms of drug toxicity.
Nowadays, herbal medicines and related research are promoted by the government level in many countries like China, India, Nigeria, The United States of America (USA) . For example, Indian government framed AYUSH ministry . The Ministry of AYUSH was formed in 2014 to ensure the optimal development and propagation of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy) systems of health care. WHO had already invested in research and development for promising medicinal plants and natural medicines. More and stringent regulatory requirements are apprehended by different regulatory authorities for the safety and efficacy point of view regarding the herbal medicinal products.
Herbal medicine becomes indispensable in modern medicine. The researchers and physicians can hardly afford to deny its utility and therapeutic efficacy. However its unwanted side effects and various health related issues are major concerns in pharmaceutical industry. To overcome this problem, the issue of various side effects of all the drugs should be addressed properly. In this review article we covered all the issues related to unwanted reaction of various photochemical which may contribute a little to the present global health knowledge and understanding.