Complementary or Alternative Plant Based Medicines and Its Active Constituents Responsible for Overall Therapeutic Efficacy

Abstract

Complementary or Alternative Medicine, like Homeopathic medicine, is made from plant, animal, and mineral kingdoms and sometimes from biochemical substances. Most of the Homeopathic remedies come from plant-based drugs. The presences of the bioactive compound in the plants are responsible for the overall therapeutic efficacy of Homeopathic medicines. The presence of bioactive compounds such as alkaloids, flavonoids, and phenols in plant drugs acts as a natural source of antioxidant substances of high importance. The concentration of these bioactive compounds and their antioxidant activity indicates that these compounds contribute to the intense antioxidant activity of Homeopathic drugs. The scope of the present research is to provide detailed information on plant-based Homeopathic medicines containing specific active compounds, which justify their typical medicinal usage in Homeopathy. It is one of the big reasons for the cure and healing properties of Complementary or Alternative Medicine medicines.

1. Introduction

One of the Complementary or Alternative medicine-based systems like Homeopathy is a belief that the body can cure itself [1]. Homeopathy developed in the late 1700s in Germany, and the two primary principles of Homeopathy are [2, 3] “Like cure likes” principles. According to this principle, patients with particular signs and symptoms are treated with homeopathy remedies that produce signs and symptoms in healthy individuals [4]. Homeopathy is a medical system devised by German physician Samuel Hahnemann (1755–1843). The first edition in which he summarized homeopathy is Organon [5]. In his first fifteen years as a physician, Hahnemann struggled a lot. One day, however, he discovered that he started taking regular doses of cinchona or the bark “which contains quinine, a medicine to treat malaria. The results produced symptoms like intermittent fever (malaria) and mild degree characteristic rigors diseases [6]. This article was first published in 1796 as an essay on a new principle for ascertaining the curative power of Drugs which was included in his famous work “The Organon of the Healing Art” [7]. Homeopathy is based on using highly diluted solutions of substances selected by matching the patient’s symptoms with the symptoms these substances produced in healthy individuals [8].

Homeopathy preparations are termed remedies and are made using homeopathic dilution, where selected substances are repeatedly diluted until the final product is chemically indistinguishable from the diluents. Homeopaths hit or shake the product in each dilution, claiming this makes the diluents remember the original substance after its removal [9]. Homeopathic medicine is made from plant, animal, and mineral kingdoms. Homeopathic medicines are made from plants such as belladonna, arnica, and chamomile, minerals such as sulfur and mercury, animal products such as Sepia, Lachesis, and sometimes biochemical substances such as histamine or human growth factor. Remedies are prepared by the process of serial dilution and succession. The greater the succession, the greater will be the potency of the remedy.

2. Homeopathic mother tincture and potencies

In homeopathy, Mother Tincture (Q) is defined as the original drug substance prepared with the aid of ethyl alcohol and water directly from the crude drug. They are the precursors of the corresponding potencies of the respective drug and the starting point for the preparation of homeopathic medicines. The original drug substance is used in extremely minute quantities to prepare a given homeopathic medicine, and the method of preparing homeopathic medicines is called potentization; in this method, one part of the original drug substance is mixed with nine parts of a vehicle (ethyl alcohol and water) and shaken vigorously by a special device that converts the preparation into the one tenth potency (1X) one tenth. On the other hand, one part of the original drug substances is mixed with 99 parts of the carrier (ethyl alcohol) is denoted as 1C potency (1:100). This process continued until the required potency is reached and homeopathic medicines are available in certain standard potencies such as 3X, 6X, 12X, 30X, 200X, 30C, 100C, 200C and 1000C etc. The potencies are nothing but energized dilutions (or attenuations) of the Mother Tinctures of homeopathic remedies [10].

In homeopathy, practitioners select a drug that would, if given to a healthy volunteer, cause the presenting symptoms of the patient example Allium cepa is derived from the common onion. While in contact with raw onion typically causes lacrimation, stinging and irritation around the eyes and nose, and clear nasal discharge. Allium cepa might be prescribed to patients with hay fever, significantly if both nose and eyes are affected.

Phytochemicals are biologically active naturally occurring chemical compounds found in plants. These phytochemical compounds are highly beneficial for human health. Generally, phytochemical compounds are classified as primary constituents and secondary constituents. The phytochemicals are generally present in the roots, stems, flowers, leaves, fruits, and seeds like various parts of the plant. This is the reason all complementary medicines are made from different parts of the plants depending upon the phytochemicals present therein to get maximum efficacy.

Chlorophylls, nucleic acid, common sugar, amino acid, proteins, and purines are known as primary constituents present in the plant. Chlorophyll forms during the photosynthesis process, responsible for giving green color to the plant. It also plays a beneficial role for humans and helps in the binding to the carcinogenic compounds in the body and inhibit their absorption in your intestine which helps to prevent their reach to our liver tissues which can cause further harm to the body.

Alkaloids, phenols, flavonoids, terpenes, lignans, steroids, glucosides, and saponins are known as secondary constituents present in the plant. Phenolic compounds are the widely distributed phytochemicals present in various parts of the plant. Flavonoids, phenolic acids, and polyphenols are the largest group of phenolic phytochemicals present in the plant kingdom. They act as strong antioxidant agents which help the human body to fight against free radical groups and protect it from free–radical mediated disease processes.

2.1 Flavonoids

Flavonoids are the polyphenolic phytochemical compounds present in vegetables, fruits, and beverages like tea, coffee, and fruit drinks [11]. Generally, flavonoids are found in conjugated form in nature and are characterized as monoglycosidic and diglycoscidic [12]. Flavonoids have many biological properties including anti-inflammatory, anti-microbial, cytotoxic, and anti-tumor activities [13].

2.2 Phenolic acids

Phenolic acids are a diverse group of hydroxyl benzoic and hydroxycinnamic acids and esters with glucose and carboxylic acid, hydroxycinnamic acid-like molecules. Phenolic acids act as a strong antioxidant agents and prevent the human body from degenerative diseases [14]. The degenerative diseases are cardiovascular disease, inflammation, and cancer. Phenolic acids have properties to act as strong antidiabetic agents [15]. Phenolic acids can influence the role of insulin and glucose receptors [16]. Phenolic compounds also have properties to inhibit the activities of α-glucosidase and α-amylase which are the main component of the conversion of dietary carbohydrates into glucose hydroxybenzoic and hydroxyl cinnamic acids [17]. Phenolic acids known for the prevention and treatment of cancer [18].

2.3 Tannins

Tannins are a group of polyphenolic compounds with a high molecular weight that can form complexes with polysaccharides, alkaloids, proteins, nucleic acid, and minerals [19]. As per epidemiological studies [20] tannins are beneficial for human health as they decrease the chance of creating chronic diseases. The tannins present in plants are used as astringent, used against diarrhea, used as diuretics against stomach problems, and duodenal tumors. Tannins have many biological properties including anti-inflammatory [21], antiseptic, and antioxidant properties. Major phenolic compounds found in various plants are quercetin, oleanolic acid, ursolic acid, kaempferol, luteolin, chlorogenic acid, curcumin, ascorbic acid, tannic acid, gallic acid [22] and, rutin etc.

2.4 Alkaloids

Alkaloids are heterocyclic nitrogen atoms naturally synthesized by a large number of organisms, including plants, animals, bacteria, and fungi [23]. Based on the type of heterocyclic ring system present in the molecule, they are pyrrolidine alkaloids, pyridine alkaloids, pyrrolidine-pyridine alkaloids, pyridine-piperidine alkaloids, quinoline alkaloids and isoquinoline alkaloids [24].

2.5 Essential oils

Essential oils are extracted from plants by a distillation process i.e. (liquid extracts), also obtained by the physically squeezed method in which essential oil squeeze out of some plants (like orange peels) in the case of flowers, extracted with a nonpolar solvent i.e. lemon oil [25].

Lemon contains essential oil like limonene, sesquiterpene, limonene, sesquiterpenes, aldehydes (citral, and citronellal), and geranyl acetate). Eucalyptusoil contains 1,8-cineol and α-pinene, and chamomile oil contains (Bisabolol oxide, Chamazulene, and α-Terpineol).

Essential oil like lemon oil is used as flavoring agent and are primarily used for adding fragrance to cosmetics, foods, or your home via a diffuser, clove oil used as an antimicrobial agent. Clove oil is used as a pain reliever such as toothache and muscle pain, kills bacteria, and is also recommended for digestive upset. Eucalyptus oil is commonly used in cold remedies like vapor rub.

2.6 Triterpenes

Triterpenes are six isoprene units like Lanosterol and squalene. Triterpenes are found in wheat germ and olives. Acyclic triterpene hydrocarbon squalene constitutes more than half of the liver oil of various species which are widely distributed in nature. These are found in fish liver oil, vegetable oil, fungi, human earwax, and sebaceous secretions.

2.7 Saponin

Saponins are secondary metabolites of the plant kingdom and are stable in aqueous solutions such as soap, hence the name “saponin” is given to these compounds. Saponins are a group of compounds that includes glycosylated steroids, triterpenoids, and steroid alkaloids. Spirostan and furostan derivatives are the two main types of steroid aglycones. The main triterpene aglycone is a derivative of oleanane. The steroidal saponins are essential precursors for steroid drugs. These steroid drugs act as strong anti-inflammatory effects for example androgens, oestrogens, and progestins [26].

2.8 Sterols

Sterols are a group of fat-like substances which occur naturally in the animal and plant kingdom. Animal sterol is known as cholesterol whereas plant sterols are known as ß-sitosterol, campesterol, and stigmasterol [27]. They have a similar structure to cholesterol. The basis of their molecular framework is a double bond. If this double bond is hydrolyzed, then the saturated plant sterols are formed from the unsaturated plant sterols.

3. Some important Homeopathic plant-based drugs and their active constituents responsible for the overall therapeutic efficacy of Homeopathic drugs

3.1 Leucas aspera

Leucas aspera (Wild) Linn, family Lamiaceae [28], is commonly called “Thumbai” [29, 30]. It is a common weed in India and is widely distributed throughout the country. L. aspera whole plant is traditionally used as an antipyretic [31] and insecticide [32, 33] drug. In homeopathy, L. aspera, mother tincture is used to treat dysentery, jaundice, fever, a bite from venomous animals [34], and enlargement of the liver and spleen. The main bioactive constituents of L. aspera are ursolic and oleanolic acid [35]. Due to the presence of ursolic [36] and oleanolic acid-like triterpenes [37], it possesses many pharmacological [38, 39] properties. L. aspera plant possesses anti-inflammatory, hepatoprotective [40], antitumor [41], anticancer [42], antimicrobial anti-HIV, antifungal, gastroprotective, hypoglycemic, and antihyperlipidemic properties (Table 1).

S. no.	Part used	Different pharmacological activity
1.	Aerial Part	Arthritis, Ulcer protective effect, Diabetes, Anticancer activity, antipsoriatic activity
2.	Leaf	Hepatoprotective activity, Cytotoxic activity, Antidiabetic activity, antivenom activity
3.	Roots	Analgesic activity, antinociceptive activity, Central nervous system depressant activity
4.	Whole plant	Cytotoxic activity, anti-inflammatory activity, Hepatoprotective activity, Antihyperglycemic activity, Antimutagenic activity, anthelminthic activity
5.	Shoot system including stem, leaves, and flower	anti-inflammatory activity

Table 1.

Leucas aspera plant parts responsible for different pharmacological activity [43, 44].

3.2 Rauwolfia serpentina

Rauwolfia serpentina (Family: Apocynaceae) is a medicinally famous herb in Homeopathy [45, 46]. Rauvolfia serpentina is therapeutically used as a sedative, a hypnotic drug, and in hypertension. Reserpine (indole alkaloid) was isolated in 1952 from the dried root of R. serpentina (Indian snakeroot) [47], which had been known as sarpagandha [48], and used for the treatment of insanity, fever, snakebites anxiety, and neuropsychiatric conditions. Reserpine has ability to deplete catecholamines [49]. Reserpine reduces glycemia in some cases, but the effect is short-lived. In some patients, it has a stimulating effect on prothrombin activity. Reserpine produces sedation and a lowering of blood pressure if administered orally, in hypertension; the impact of Reserpine is slow, seldom appearing before 3–6 days of administration and continuing for some time after the withdrawal of the drug a cumulative effect. It is most valuable in young patients with mild labile hypertension and tachycardia. In long-established hypertension, it is best used in conjunction with more potent hypertensive drugs such as hexamethonium or hydralazine. Combined with polythiazide; it is a useful hypertensive in mild to moderate thiazide, it is a useful hypotensive in mild to moderate conditions. The response to Reserpine varies in patients, and the dosage must be adjusted to individual requirements. In severe hypertension, it may be given by intravenous or intramuscular injection when the effect begins within a few hours. Parenteral therapy of Reserpine is indicated in the treatment of hypertension only when oral administration is impracticable [50]. Different alkaloids are present in Rauwolfia, viz. ajmaline, ajmalinine, ajmalicine, scrpentine, and serpentinine [51]. Reserpine, yohimbine [52], recinnamine, reserpinine, rauwolfinine, renoxidine, rescin-namine, reserpiline, sarpagine, serpentinine, tetraphyllicine, 3-epi-a-yohimbine. It also contains small amounts of phytosterol and fatty substances [53]. R. serpentina is one of the essential drugs for various disorders, including hypertension (Table 2).

S. no.	Alkaloid	Different pharmacological activity
1.	Reserpine	Antipsychotic activity and antihypertensive activity
2.	Reserpiline	Antihypertensive activity
3.	Rescinnamine	Antihypertensive activity
4.	Ajmaline	Antiarrhythmic activity
5.	Ajmalicine	Vasodilator
6.	Serpentine	Tranquilizer
7.	Alstonine	Antipsychotic activity

Table 2.

Rauwolfia serpentina major alkaloids responsible for different pharmacological activity [54].

3.3 Digitalis purpurea

Digitalis purpurea, commonly known as Foxglove [55], is a biennial plant belonging to the family Plantaginaceae. It is indigenous to part of western and southwestern Europe. In India, Digitalis purpurea is found in the Nilgiri hills of Tamil Nadu, southern Sikkim, and the eastern Himalayan region. Its leaves contain both primary and secondary glycosides. Digitoxin is the main active constituent of the D. purpurea plant, which is used as cardiac glycoside in medicines. Digitoxin is generally known as a highly toxic by-product [56]. In Homeopathy, D. purpurea is used for treating heart-related diseases where the heart is primarily involved where the pulse is weak, irregular, intermittent, abnormally slow, and dropsy of external and internal parts. In females, during labor-pain in the abdomen and back before menses, and for uterine hemorrhage [57] D. purpurea homeopathic medicine is recommended in Homeopathy. As per the information given in the homeopathic book Materia Medica Pura, D. purpurea is mainly used for diseases where the heart is primarily involved [58], such as atrial flutter, atrial fibrillation, and in case of congestive heart failure conditions. Cardiac glycosides [59], such as digitoxin in the leaves of D. purpurea [60], help to prevent congestive heart failure by increasing the force of contractions of the heart in the body. In previous suggested studies, digitoxin present in the leaves of Digitalis has the highest gastrointestinal (GI) absorption of 90–100% with a half-life of 4–5 days [61] which is more significant than other commercially available cardiac steroids such as Digoxin, Deslanoside, Ouabain [62]. D. purpurea, being rich in active constituents, shows cardiovascular, cytotoxic [63], antioxidant, anti-diabetic [64], insecticidal, immunological, cardioprotective, hepatoprotective, and neuroprotective effects and has greater importance in Homeopathy.

3.4 Hydrocotyle asiatica

Hydrocotyle asiatica, synonym Centella asiatica commonly known as brahami, belongs to the family of perennial plants in the flowering plant Umbelliferae (Apiaceae) [65]. H. asiatica is an essential Homeopathic medicinal plant widely used as a medicine due to the benefit of its bioactive compounds such as asiatic acid [66], rutin, kaempferol, quercetin, gallic acid, luteolin, and catechin [67]. Hydrocotyle asiatica possess diverse pharmacological activities such as neuroprotective, nerve regenerative, immunomodulatory, anti-depressive, memory enhancing [68], gastroprotective, cardioprotective, radioprotective, anti-cancer, antimicrobial, anti-inflammatory, anti-diabetic and antioxidative properties. H. asiatica contains the most abundant triterpene glycoside asiatic acid, which shows cytotoxic activity on cancer cells. Asiatic acid is a triterpene glycoside, commonly used for wound healing. Asiatic acid has antioxidant, anti-inflammatory, and neuroprotective properties. H. asiatica has been used in folk herbal medicine for centuries for memory enhancement, antidepressants [69], wound healing [70] and psoriasis remedy [71], and chronic disease treatments [72]. In homeopathy, H. asiatica acts as a curative in disorders that exhibit interstitial inflammation, cellular proliferation, leprosy, lupus, granular ulceration of the womb, profuse leucorrhœa, psoriasis gyrates, and syphilitic affections [73].

3.5 Nux vomica

Nux vomica, commonly known as Kuchla, belongs to the family Loganiaceae. In homeopathy, N. vomica seed part is used. N. vomica is one of the most prescribed medicines in homeopathy [74]. The main bioactive compounds of N. vomica seeds are strychnine and brucine. Brucine in N. vomica is responsible for its anti-tumor, anti-inflammatory, analgesic, and effects on the cardiovascular and nervous systems. The presence of brucine makes N. vomica an analgesic agent and can be used to relieve arthritis and traumatic pain [75]. The alkaloids in N. vomica seeds are protostrychinine, isostrychinine, vomicine, n-oxystrychinine, pseudostrycheinine, chlorogenic acid, and glycoside. In the homeopathy system of medicine, N. vomica is prescribed for anger effect, colic, constipation, dyspepsia, gastrodynia, hemorrhoids, tobacco habit, insomnia, nightmares, lumbago, diabetes, asthma, aphrodisiac and to improve appetite [76]. N. vomica has an anti-alcoholism effect. In homeopathy, Nux vomica 30C, 200C, and 1000C are recommended for anti-alcoholism effects [77]. In recent years brucine displayed an excellent anti-tumor effect on various tumors. For hepatocellular carcinoma, brucine inhibits the proliferation of Hep G2 cells by regulating calcium concentration and depolarization of mitochondria [78].

3.6 Matricaria chamomilla

Matricaria chamomilla is, commonly known as chamomilla and belongs to the Asteraceae family which is referred to as the star among medicinal species. M. chamomilla was introduced in India during the Mughal period. In India, M. chamomilla is grown in Punjab, Uttar Pradesh, Maharashtra, Jammu, and Kashmir [79]. In Homeopathy, M. chamomilla part used is the whole plant. The whole chamomillaplant contains over 120 constituents [80]. M. chamomilla acts as a natural antioxidant and antimicrobial agent. The latest research has proved the presence of 52 active components in the M. chamomilla plant in which the highest contents are β-farnesene α-farnesene, α-bisabolol, and its oxide chamazulene, germacrene, and spiroether [81]. M. chamomilla homeopathic extracts contains active groups of phenol, flavonoids, and coumarins. It act as strong antioxidant, antibacterial, antifungal, antiparasitic agents [82]. In general, M. chamomilla is used for many ailments in humans such as fever, inflammation, menstrual disorder, insomnia, and ulcers; very good in wound healing, muscle spasms, gastrointestinal upset, rheumatic pain, and hemorrhoids [83]. This plant has immense curative properties. In Homeopathy, M. chamomilla is used for tooth problems in infants [84]. The symptoms are twitching, convulsion during teething, intolerant pain, frantic irritability, ugly, cross, uncivil, quarrelsome, and colic after anger [85].

3.7 Aconitum napellus

Aconitum napellus belongs to the family Ranunculaceae, commonly known as Monkshood. The main active constituent present in A. napellus is “aconitine”, which is present throughout the plant, with incredibly high levels in the leaves and roots. In homeopathy A. napellus plant part used is the whole plant. A. napellus plant contains various diterpenes alkaloids, isonapelline, luciculine, and napelline [86]. Aconitine present in A. napellus acts as a voltage-gated sodium channel activator. These sodium channel act as transmembrane proteins that are responsible for the rapid depolarization that underlies the upstroke of action potentials in neurons and is responsible for crucial nerve impulse conduction [87]. A. napellus has solid neuroprotective properties. A. napellus is a constituent of Ayurvedic, Unani medical preparation, and polyherbal formulation to treat diabetes, as a nerve tonic with potent antioxidant properties [88]. A. napellus is very useful in numbness [89], a sensation of cold, and pain in the extremities, associated with diabetic neuropathy, and is also used for the treatment of rheumatoid and joint pain [90]. A. napellus is the first homeopathic medicine that is recommended for the onset of acute croup [91]. In homeopathy, A. napellus is used in case of shock, sudden or violent onset ailments from shock, fright or fear, intense fear, terror-struck, restlessness with fear of death and diseases from exposure to cold and dry wind [92].

3.8 Rhus toxicodendron

Rhus toxicodendron synonym Toxicodendron pubescens is commonly known as poison ivy and belongs to the Anacardiaceae family [93]. This plant family produces the chemical substance pentadecylcatechols. The main active constituent in R. toxicodendron is fisetin, rhamnose, and gallic acid [94]. This plant’s main habitat is in the forest of the United States. In Homeopathy, the leaves part is used. In Homeopathy, R. toxicodendron is used for joint pains [95], stiffness worse in damp weather, irritability, restlessness [96], back pains, and asthma alternating with skin eruptions [97]. R. toxicodendron is used for anti-inflammatory activities for arthritis [98] and rheumatism [99]. In homeopathy, Rhus tox 6C, 12C, 30C, and 200C are recommended [100]. R. toxicodendron retains its anti-arthritis properties at 1 M (potency 1000C), 10 M (potency 10,000C), and CM (potency 100,000C) homeopathic dilution [101]. R. toxicodendron also possesses immune stimulatory activity in its crude form and in homeopathically diluted forms [102]. It is commonly used for strains [103]. This medicine is recommended for patients with high fever and body aches and restlessness problems. A person experiencing this type of fever might want to remain in motion throughout to avoid restlessness. This medicine is recommended in case a person catches a fever due to getting wet in the rain [104].

4. Conclusion

Homeopathic medicines show high therapeutic efficacy and synergetic effects due to the presence of many active constituents in the plants, which altogether cause synergetic effect and are responsible for the overall therapeutic efficacy of the homeopathic drug. There is an essential need for physicochemical, phytochemical, and High-Performance Thin Layer Chromatography studies of homeopathic medicines to laid down the standard for a monograph of pharmacopeia standards. In the future, these studies may open the area of vast research opportunities in medicinal plant biochemistry. The quantitative estimation of homeopathic drugs should be carefully evaluated and quantified to determine the presence of active compounds in these drugs, responsible for the overall pharmacological activity of the homeopathic medicine. The presence of alkaloids, flavonoids, and phenols in plant drugs act as a natural source of antioxidant substances of high importance in homeopathic medicine. The concentration of these active compounds and their antioxidant activity indicate that these compounds contribute to the intense antioxidant activity of Homeopathic medicine. The presence of active constituents in homeopathic mother tincture suggests that the mother tincture of homeopathic plant drugs contained specific active compounds which justify typical medicinal usage in Homeopathy and the reason for a cure and healing properties for homeopathic medicines.