Comparative Study between Herbal and Synthetic Antidepressant Drugs

Abstract

According to the WHO report approximately 450 million people suffer from mental and behavioural disorder. Depression is one of the most common neurodegenerative disorders which arise due to the imbalance of neurotransmitters release at the synaptic cleft. A large number of synthetic drugs are being used as standard treatment for depression, they have many adverse effects that a limit the therapeutic treatment. Traditionally herbs are used for the treatment of depression which may offer advantage in terms of safety and tolerability, possibly by improvement in patient compliance. Herbal drugs are more commonly used because these have small amount of chemicals, these produced less side effects than standard drugs. Overall, this chapter presented an overview of the research that has been done on the many herbs, Mechanism of action involving monoamine reuptake, neuroreceptor binding and channel transporter function, and neural communication or HPA modulation. Several pharmaceutical companies are working on “triple” reuptake inhibitors that stop all three monoamines from being reabsorbed. Studies into the interplay of monoamine systems with other neurotransmitters (e.g., CRF, neurokinins, glutamate, and GABA etc.) will aid in the development of realistic, integrated neurochemical models of depression.

1. Introduction

Depression is a weakening disease and it is mostly affecting modern society. The world health organization forecasts that in 2022 depression will become the major common cause of loss of interest in the working in the entire world. Thus the research of depression is one of the most important way through which we can obtain new treatment of depression and improve the developed drugs which can work better for depressive individuals. It will also assist to develop and create new approaches that will be used for better treatment of depression. Chemical transmission is the major tool through which nerves communicate with each other. Now it is well known that the presynaptic and postsynaptic events are responsible for the plasticity and learning within the Central nervous system. Chemical transmission requires different types of steps including synthesis of the neurotransmitters, their storage in secretary vesicles, and their release into the synaptic cleft between presynaptic and postsynaptic cleft. The initial step of the synthesis of neurotransmitters is the facilitated transport of amino acids from blood to the brain, in the brain precursors are converted into neurotransmitters enzymatically. These are stored in the synaptic vesicles, and finally released into the synaptic cleft via calcium dependent process. The release rate of neurotransmitters determined the rate of firing of neurons which means that the drug alter the firing rate of neurons. This modification of neurons carried out the alteration of release of neurotransmitters. After this released neurotransmitters bind with somatodendritic auto receptors. Thus binding of neurotransmitter to auto-receptors is responsible for reducing the synthesis of neurotransmitters or additional release from the presynapse. The synaptic results of neurotransmitter are ceased via binding with specific receptors and reuptake into the pre-synapse. Neurotransmitters metabolized by monoamine oxidase enzymes in the presynapse [1].

2. Plant profile

Achyranthes aspera (family-Amarantheceae) is commonly known as Latjira in Hindi. The plant is used for the treatment of dysentery, fever and diabetes [2]. A. aspera is available as weed in whole India, Asia and many other parts of the world such as Mexico, Central America and Africa [3]. It is described as bitter, pungent, purgative, heating, laxative, stomachic, carminative and digestive and is also used for the treatment of bronchitis, heart disease, piles, itching abdominal problems, ascites, rheumatism, abdominal enlargement, rabies and also for enlarged cervical gland. It is use as folk medicine. It is also known as medicinal herb in different types of system of medicine in India. It is known by different names such as Chirchita (Hindi), Apamarg (Sanskirt), Aghedi (Gujrati), Apang (Bengali), Nayurivi (Tamil), Kalalat (Malayalam) [4]. This plant grows on road sides. It is also found as field boundaries and waste places as a weed throughout India up to an altitude of 2100 m and in South Andaman Islands [5]. The leaves extract of A. aspera having antifertility effect [6]. Methanolic extract of A. aspera shows wide varieties of pharmacological activities however, little is known about its anti-depressant activity. Most of the researches are not found its antidepressant activity by using open field test and forced swimming test, so the aim of present study to assess the anti-depressant activity of A. aspera extract against physically induced depression in rats, using open field test and forced swimming test apparatus [5]. A. aspera (Chirchita) belong to the family Amaranthaceae. Two different varieties of A. aspera are mentioned in Ayurvedic and Chinese medicines, 1st is red and 2nd is white [2].

Common name of A. aspera: [7].

Arabian: Atkumah, Na’eem, No’eem, Mahout, Wazer (Yemen).

Ayurvedic: Apamarg, Chirchita, Shikhari, Shaihkharika.

Bengali: Apang.

English: Prickly chaff flower, Hawai chaff flower, Devil’s horse whip.

French: Achyranth a feuillers rudes, collant, Gendarme.

Gujrati: Safad Aghedo, Anghadi, Andhedi, Agado.

Hindi: Latjira, Chirchita, Lamchichra, Sonpur, Onga.

Indonesia: Jarong.

The methanolic extract of A. aspera showed the anxiolytic activity due the presence of its phytoconstitents viz. alkaloid, steroid and triterpenes. It could be used for the management of anxiety disorders because it is economically therapeutic agent [8]. Seed extract of A. aspera give the hypolipidemic activity which might be attributed to its phyto-constituents like saponin and flavonoids. Thus it showed the protective effect against HFF [9]. Leaves and stem parts of the A. aspera were converted into powder form and extracted with distilled water, which extract exhibited antimicrobial activities because of its many photochemical constituents including flavonoids and alkaloids [10]. The root extract of A. aspera has anticancer activity against different human cancer cell lines due the presence of its chemical constituents like alkaloid, flavonoids, phenolics and terpenoids [11]. The methanolic extract of it possess antiviral (antiherpes) activity because of its pure compound oleanolic acid. The OA of A. aspera showed the protective effect against both HSV-1 and HSV-2. Result showed that OA or methanolic extract of Acyrantes aspera act on the early stage of HSV replication [12]. It was also reported that its phytoconstituent (non- alkaloid fraction) significantly inhibits Epstein–Barr-virus which is a member of Herpesviride family [13]. The ethanolic extract of A. aspera seeds showed significant anti arthritic activity at various concentrations ranging from 10 to 1000 μg/ml [14]. The brewer’s yeast induced pyrexia in rats used for the investigation of antipyretic activity of A. aspera extract. Regulation of body temperature requires a balance between production and loss of heat. The hypothalamus acts as a regulator for the set point at which body temperature is maintained [15]. The antiulcer activity of A. aspera demonstrated that the methanolic extract of A. aspera protects rats against ulcer by using pyloric ligation method. From the result it has been clear that the methanolic extract of A. aspera at a dose of 300 mg/kg shows maximum ulcer protection as compared to control group [16]. A. aspera contain different chemical constituents such as alkaloids, flavonoids, saponins, steroids and terpenoids. Its water soluble alkaloid achyranthine isolated via extraction possess anti-inflammatory activity [17]. The result showed that the ethanolic extract of A. aspera having antifertility activity. It also possesses the antizygotic, blastocytotoxic and antiovulatory activities [18]. Antiarthritic activity of A. aspera has been carried out by using most popular method, known as inhibition of protein denaturation. The ethanolic extract of A. aspera seeds showed significant anti-arthritic activity of various concentrations ranging from 10 to 1000 μg/ml [14]. Alkaloids of leaves of A. aspera plant determined with the help of thin layer chromatography. In this method silica gel aluminum used as stationary phase while chloroform used as mobile phase for the determination of alkaloids in the leaves of A. aspera. Measurement of alkaloid in the alkaloid fraction extract of leaves of A. aspera carried out using high-performance liquid chromatography. Alkaloids of A. aspera extract used for the treatment of different disorders such as in-vivo study of it demonstrated that the alkaloid of A. aspera cause apoptosis and healing in breast cancer cells in mice induced by benzopyrene. A. aspera consist of 13 different types of chemical constituents while alkaloids are major constituents of it. 53.36% alkaloids are present in the A. aspera [19].

3. Description and Distribution

A. aspera is a medicinal plant. It is found throughout India as an annual herb. It is also found in Asia and many parts of world such as Mexico, Central America and Africa. A. aspera consist of many antioxidants like alkaloids, terpenoids and saponins, which have various pharmacological properties. Different types of chemical constituents have been isolated from this plant by various techniques. All pharmacological properties and chemical constituents are used for the treatment of various human diseases. A. aspera globally available as a medicinal weed in Baluchistan, Ceylon, Tropical Asia, Africa, Australia and America. It is also present Shiv Bari and Himachal Pradesh. In India it is found in field boundaries and also present at the road sides. The plant grows to a height of 0.2 to 2.0 m. root is cylindrical, 0.1–1.0 cm in thickness. Root is yellowish- brown in color, which is of two types secondary and tertiary. Stem is square in shape and yellowish-brown in color. Leaves are simple, slightly acuminate, petiolate and ovate. Leaves contain anomocytic type of stomata on the lower epidermis. Flower is 8–30 cm long and 3–7 mm wide. It is bisexual greenish-white. It consists of 5 perianth segment, 5 stamens, short filament, 7 gynoecium bicarpellary, syncarpous, ovary superior, single ovule, style and single stigma. It is found in two different color red and white flower. Seeds are round at the base, which are brown in color [7]. The whole plant and seeds of A. aspera consist of an alkaline substance known as potash [20]. It is common herbal drug in Ayurvedic, Unani-Tibbi, Siddha, Allopathic, Homeopathic, Naturopathic and Home remedies [21]. It is useful for the treatment of cough, renal dropsy, fistula, scrofula, skin rash, nasal, infection, chronic malaria, impotence, fever, asthma, piles and snake bites [22].

4. Chemical constituents

A. asperaconsist of different types of phytochemicals such as alkaloids, tannins, cardiac glycosides, steroids, flavonoids, terpenoids, reducing sugar and saponins. Saponins include ecdysterone, 20-hydroxy-ecdysone [23]. It consists of alkaloids such as three bisdesmosidic saponins (I-III), 20-hydroxyecdysone, quercetin 3-O-β-d-galactoside [24]. It possesses triterpenoids, which are β-d-glukopyranosyl-13-β-[O-α-l-rhamnopyranosyl-(1 → 3)-O-β-d-glucopyrauronosyloxy] machaerinate [25]. It is also a good source of ketones, including 36, 37-dihydroxyhenpentacontan-4-one, triacontanol, 36,47-dihydroxyhenpentacontan-4-one [26, 27]. Pentatriacontane, 6-penta-tri-acontanone, Hexa-triacontane, tritriacontane, these are found in the stem of A. aspera [27]. Leaves and stem leaves consist of different types of chemical constituents such as 20-hydroxy ecdysone, quercetin-3-O-β-d-galactoside, P-benzoquinone, hydroquinone, spathulenol, nerol, asarone and eugenol [28, 29]. Seeds of A. asperacontains a number of d-glucoronic acid, β-d-galactopyranosyl ester of d-glucoronic acid, oleanolic acid, amino acid, hentriacontane, 10-tricosanone, 10-octacosanone and 4-tritriacontanone [30]. It is also consist of various type of cyclicchain aliphatic fatty acids, fatty acid composition (lauric, myristi, palmitia, stearic, arachidic, behenic, oleic and linoleic acid) and oleonolic acid glycosides [α-l-rhamnopyranosyl-(1 → 4)-(β-d-glucopyranosyluronic acid)-(1 → 3)-oleonolic acid, α-l-rhamnopyranosyl-(1 → 4)-(β-d-glucopyranosyluronic acid)-(1 → 3)-oleonic acid-28-O-β-d-glucopyranoside [31, 32].

Acyranthine a water soluble alkaloid present in the A. aspera is responsible for various type of pharmacological activities like dilation of blood vessels, lowering of the blood pressure, depression of heart and increase the rate and amplitude of respiration. It is also consisting of another water soluble alkaloid known betain. Betain is isolated from the whole plant [33].

5. Medicinal uses

A. aspera shows a wide spectrum of pharmacological activities such as bitter, pungent, heating, laxative, stomachic, carminatives and improve appetite as well as useful in vomiting and heart disease. It is also used in various types of disease like pile, itching, abdominal pains, dyspepsia, dysentery and blood disease [34]. It is widely used for the treatment of many disorders, which are asthmatic cough, snakebite, hydrophobia, urinary calculi, rabies, influenza and gonorrhea. Its dried leaf powder mixed with honey is useful for the treatment of early stage of asthma [35]. Naayuruvi kuzhi thailum has been identified that Acyrantes aspera as the primary constituent comes under the Siddha system, which is used in the management of asthma [36]. Traditionally, this plant is used in the treatment of asthma and cough [37]. The root of A. aspera is used in whooping cough, tonsillitis [38, 39].

6. Pharmacological activities

The literature survey has shown that following pharmacological action of A. aspera.

6.1 Anti-parkinsonism activity

Parkinson disease is arising due to the degradation of dopamine- carrying neurons in the substantia nigra. The neuronal death occurs in PD is due to the damage of free radicals and lewy’s bodies formation [40]. Levodopa is used as the first line drug for the treatment of Parkinson disease [41]. Powder of the whole plant of A. aspera is extracted by using hydro-alcoholic solvent and its get evaporated to a concentrate by rotary evaporator at 40°C [42]. 24 rats were divided into four groups (n = 6). Hydro-alcoholic extract at a dose of 200 and 400 mg/kg was administered to the rats before 30 minutes of haloperidol treatment for 20 days. In a study of anti-parkinsonism activity, the ant-parkinsonism effect of hydro alcoholic extract of A. aspera on haloperidol which is administered at a dose of 2 mg/kg via intraperitoneal route induced catatonia in rats. In haloperidol treated rats the motor coordination was studied by using rotarod test and hang test. The increase degree of catalepsy in haloperidol treated group was measured after 60 and 90 minutes of administration. The result has shown score of catalepsy was significantly decreased after 60 minutes with the test drug HA at a dose of 200 and 400 mg/kg. It is also demonstrated that group exhibited maximum reduction in the catalepsy, which is treated with 400 mg/kg. The results of rotarod test show that the retention time was reduced in the haloperidol treated group. The retention time significantly improved in HA treated group. Among these groups, maximum retention time was noted in the 400 mg/kg treated group [43].

6.2 Anxiolytic activity

Anxiolytic activity of A. asperais due to the presence of its phytochemical constituents such as alkaloids, steroids and triterpenes. Benzodiazepines are the first line drug for the treatment of anxiety but these have lots of side effects like sedation, muscle relaxation, anterograde amnesia and physical dependence [44]. Methanolic extract of A. aspera was administered to the different groups (100, 300 and 600 mg/kg) by using different apparatus, hole board, open field, elevated plus maze and light dark test. Animals were treated with methanolic extract at a dose of 100, 300 and 600 mg/kg, p.o. shows significant and dose dependent increase in the number and duration of head poking as compared to control group. In open field test, animals treated with methanolic extract of A. asperaat a dose of 100, 300 and 600 mg/kg, p.o. in this test there was significant (p < 0.01) increase in rearing. The number of squares traveled by the animals also significantly (p < 0.01) increased when animals treated orally with methanolic extract of A. aspera at 300 and 600 mg/kg. Thus result was indicating a dose dependent anxiolytic activity of the plant extract. There was also significant (p < 0.01) increase the number of entries and time spent in the open arm of elevated plus maze of methanolic extract treated group at 100 to 600 mg/kg. Diazepam used as a standard drug. In the close arm of elevated plus maze, number of entries and time spent significantly (p < 0.01) decrease as compared to control group. The group of animal administered 600 mg/kg of methanolic extract of A. aspera was demonstrated higher number of entries and time spent in open arm than the standard drug. In the light and dark test, animals treated with methanolic extract of A. aspera at 300 and 600 mg/kg dose indicated significantly (p < 0.01) increase the time spent in lighted box, number of crossings and transfer latency. In the dark box significantly (p < 0.01) decrease the time spent [8].

6.3 Hypolipidemic activity

Alcoholic extract of the entire plant of A. aspera demonstrated hypoglycemic activity. Rats were divided into four groups each containing six animals. Consumption of fructose is responsible to increase body weight as a result of decreased insulin level in the blood. It is also responsible to decreased leptin production followed by an increase in the circulating nonesterified fatty acids, which decrease insulin sensitivity due to increasing the intramyocellular lipid content [45]. In the present study it was found that the HFF significantly increased TGL [46]. Saponins constituents of A. aspera extract are reported to increase the lipoprotein lipase which is responsible for the removal of circulating free fatty acids that results decrease the total cholesterol [47]. It is also reported saponins are effective as HMG-CoA reductase inhibitors [48]. It has reported that 100 mg/kg of A. aspera administered to the rats significant (p < 0.001) decrease in the level of VLDL and LDL with an increase in the levels of HDL were observed [9].

6.4 Antiulcer activity

Gastric ulcer is a pathological condition caused due to the imbalance between aggressive factors, such as gastric acid, pepsin, stimulation of vagus nerves, secretion of gastrin and increase in the number of parietal cells and protective factors like bicarbonate ion, mucus productivity, mucus secretion and prostaglandins. Literature survey has shown that its chemical constituents like flavonoids and triterpenoids are responsible for antiulcer activity [49]. The root part of A. aspera was extracted with methanol. Ulcer was induced by pylorus ligation method. Ranitidine is used as the standard drug for the comparison of methanolic extract of A. aspera. 300 mg/kg dose of MEAA showed 91.89% antiulcer activity. From the result it has clear that 300 mg/kg dose of MEAA shows maximum antiulcer activity than the control group. The lower dose of MEAA does not show antiulcer activity but at higher dose it shows ulcer protection activity [16].

6.5 Diuretic activity

Diuretics are the drugs which are used to increase the rate of urine flow. These are used to adjust the balance of body fluid [50]. It is reported that it consists of alkaloids, flavonoids, saponins, steroids and terpenoids [17]. The aqueous and alcoholic extract of leaves of A. aspera showed good diuretic activity. In this study it has clear that urine volume, cation and anion excretion was found to be increased, Na⁺/K⁺ ratio of 2.04 and 2.18 were obtained for aqueous and alcoholic extract respectively while the normal value for Na⁺/K⁺ ratio is reported to be 2.05–2.83 [51].

6.6 Antidiabetic activity

Diabetes is one of the most common disorders. About 30 million people suffer from diabetes in the world. It is occurring due the imbalance secretion of glucose and insulin. Insulin is used for maintaining blood glucose level. It is characterized by high blood glucose level, weight loss, extreme thirst and weakness. Alloxan administered to the animals for inducing diabetes. Alloxan administered to the animals for 30 days continuously. Animals were treated with ethanolic extract of A. aspera the blood glucose level was found to be increased by 123% and 128% on the 15th and 16th day of exposure respectively. After completion of exposure period the blood cholesterol level decrease was found to be 5.5% [52].

6.7 Antifertility activity

Protective effect of ethanolic extract of A. aspera against fertility is now being investigated including antizygotic activity, blastocytotoxic activity and abortifacient activity. The results showed the extract of A. aspera having antifertility and antiestrogenic effect in female rats. Administration of ethanolic extract of A. aspera to the animals at a dose of 200 mg/kg and 400 mg/kg significantly decrease in the duration of estrous & metesterous phase. Treated the animals with ethanolic extract of it at a dose of 200 and 400 mg/kg reduced the weight of ovaries than the control group [18].

6.8 Anti-inflammatory activity

The leaves of A. asperaare used for the treatment of dermatoligical disorder [53]. It was investigated that alcoholic extract of A. asperahas potential anti-inflammatory effect in Wistar rats at different doses such as 50, 100 and 200 mg/kg. Anti-inflammatory effect of A. aspera extract carried out by using carrageenan-induced paw edema (acute inflammatory model) and cotton pellet granuloma test (chronic inflammatory model). All the doses of alcoholic extract of A. aspera tested in carrageenan-induced paw edema caused a significant (p < 0.05) and decreased paw edema 32–40.5 compared to control group. In cotton pellet granuloma model, the concentration of A. aspera (50, 100 and 200 mg/kg) caused a significant (p < 0.05) and marked inhibition 34.6% of granuloma weight as compared to control group [54].

6.9 Antipyretic activity

In a study of anti-pyretic activity of crude extract of A. aspera was carried out by brewer’s yeast-induced pyrexia in rats. Initially rectal temperatures were recorded. Administration of the yeast at a dose 10 mg/kg to the rats produced significant increase in rectal temperature 24 hours after yeast injection [55]. The methanolic extract of leaves of A. aspera consist of alkaloids, steroids, proteins, flavonoids, saponins, mucilage, carbohydrates and tannins. The methanolic extract was administered orally to different groups at a dose of 100 and 200 mg/kg by intra-peritoneal route. 0.3 ml of normal saline was administered to the control group. Paracetamol (150 mg/kg) used as a standard drug. The methanolic extract of A. aspera demonstrated significant (p < 0.01) antipyretic activity. The dose at a 200 mg/kg extract has shown a good antipyretic activity (p < 0.01) with all the doses used when compared to the control group [15].

6.10 Anthelmintic activity

Helminthiasis is one of the most popular disease and one of the most serious diseases [56]. Stem powder of A. aspera extracted with methanol and water. It was extracted by using maceration process. Its chemical constituents such as saponins A, saponins B, terpenoids and volatile oils showed anthelmintic activity. Albendazole used as a standard drug for the comparison of anthelmintic activity of A. aspera. Extract of it’s used at different concentration (2.5, 5, 10 and 20 mg/ml) for testing anthelmintic activity which based on the determination of time of paralysis and time of death of the worms. All the methanolic extracts of A. aspera showed the better protection against the helminthiasis [57].

6.11 Antibacterial activity

Phytochemical components of A. aspera like flavonoids and alkaloids showed the antibacterial activity [58]. It is used for the treatment of urinary tract infections [59]. Five bacterial species used as a testing organism including Pseudomonas aeruginosa, Proteus mirabillus and Enterococcus faecalis. The leaf and stem of the A. aspera was extracted with organic solvent. 5 mg/ml concentration of the extract used as a testing agent and their activity measured by the determination of zone of inhibition as produced by antibiotic sensitivity method on Mueller-Hinton agar [10].

6.12 Antifungal activity

The antifungal activity of A. aspera was obtained by using aqueous & ethanolic extract of root of its. Clotrimazole (1% w/w) used as standard drug for the comparison of A. aspera extract. The study is carried out to determine the antifungal activity of the A. aspera root extract by agar well diffusion method [60]. Antifungal activity was obtained through the sabouraud dextrose agar medium against culture of Trichophyton rubrum. The microorganism containing culture was inoculated and these inoculated plates were maintained for 2 hours at room temperature to allow diffusion of the solution into the medium. These petridishes incubated 25° ± 1 for 7 days [61]. Antifungal activity determined through the inhibition of diameters of zone surrounding each of the walls. The result has shown that the zone of inhibition of ethanolic extract is 23 mm and zone of inhibition of aqueous extract is 19 mm taking 10 mg/ml of extract. Ethanolic extract of Achyranthesaspera shows good antifungal activity against Trychophyton rubrum than the aqueous extract [62].

6.13 Antiviral activity

Different types of compounds obtained from plant origin have been shown to exhibit antiviral activity against some virus including herpes simplex virus those chemical constituents which are having antiviral activity includes alkaloids, flavonoids, tannins, terpenes, saponins, quinines, polysaccharides, steroidal glycoside proanthocyanidin and proteins [63]. Herpes simplex virus is of two types HSV-1 and HSV-2. Acyclovir has been used for the treatment of viral disease since 1970 [64]. Other types of antiviral drugs used such as ganciclovir, foscarnet and cidofovir that target herpes-virus DNA polymerases [65]. In the study it was evaluate that the methanolic extract of A. asperahaving antiviral activity. Its constituent oleanolic acid also possessed antiherpes activity. The methanolioc extract of A. asperawas found to be weak anti-herpes activity (EC₅₀ 64.4 μg/ml for HSV-1 and EC₅₀ 72.8 μg/ml for HSV-2). On the other hand, oleanolic acid possessed potent anti-herpes virus activity against both HSV-1 (EC₅₀ 6.8 μg/ml) and HSV-2 (EC₅₀ 7.8 μg/ml) [12].

6.14 Other activities

Study shows the hydro-ethanolic, n-hexane and chloroform extracts of root of A. aspera were found to be effective for sperm immobilization, sperm validity and nuclear chromatin decondensation [66]. It has been demonstrated that the ethanolic extract of root of A. asperaplant exhibits post coital antifertility effect in female albino rats. According to their experimental study, the ethanolic extract of A. aspera at a dose 200 mg/kg showed 83.3% anti-implantation effect [67]. The methanolic extract of leaves of A. aspera is responsible for cancer chemo protective action. It is consisting of different chemical constituents, including alkaloid, non-alkaloid and saponins. It is demonstrated that the methanolic extract of A. aspera allow nephroprotective activity against lead acetate induced nephrotoxicity in male albino rats [68]. The research showed that ethanolic extract of A. aspera produce broncho-protective effect against toluene diisocyanate induced occupational asthma in wistar rats. In this the total and differential leucocytes count was carried out in blood and bronchoalveolar fluid. It is revealed that A. aspera treated rats did not show any airway abnormality [69]. Acyranthine, it is water soluble constituent of Acyrantes aspera which decreased blood pressure and heart rate. It is also responsible dilation of blood vessels and increased the rate and amplitude of respiration in dogs and frogs. The contractile effect of acyranthine alkaloid was found to be at 0.5 mg/ml on frog rectus abdominal muscle was less than that of acetylcholine (0.1 mg/ml) [33]. It is exhibited that the petroleum ether extract of A. asperaat a dose 200 mg/kg shows protective effect against allergic reaction in both milk induced leukocytosis and milk induced eosinophilia in mice. The antiallergic activity of A. aspera was found to be due to the presence of steroids such as β-sitosterol, ecdysone and ecdysterone [70]. It is demonstrated that the ethanolic and aqueous extracts of A. aspera used for wound healing activity. The wound healing activity was carried out by using two experimental wound models, first is excision wound model and second is incision wound model [71]. It has been demonstrated that stem extract of A. aspera shows anti-plasmodial effect [72].

7. Synthetic drugs

7.1 History of antidepressants

In the late 1940s two scientist Hafliger & Schindler were synthesized a series of more than 40 iminodibenzyl derivatives which are possibly used as antihistamine, sedatives, analgesics and anti-parkinsonism drugs. Out of this imipramine was found to be a dibenzazepine compound, which is different from the phenothiazines because of replacement of the sulfur with an ethylene bridge to produce a seven membered central ring analogous to the benzepine antipsychotic agents [73]. During clinical investigation of these phenothiazenes analogs, Kuhn was found to be imipramine relatively ineffective for the treatment of psychosis but it had a remarkable effect for the treatment of depression [74]. Tricyclic antidepressants showed quinidine like effect on cardiac conduction that can be harmful at overdose and these are used limited for the heart patients. This is the main reason that TCAs only limited used to the patient at any given time. The research of chemically related compound to imipramine was found to be multiple analogs that are common in clinical use in the United States. There were also yielded diabenzazepines, imipramine and its secondary metabolite desipramine, as well as its 3-chloro derivative cloimipramine, amitriptyline and its N-demethylated metabolite nortriptyline, doxepin (dibenzoxepine) and protriptyline. Dibenzazepines are similar to the phenothiazines chemically. The ethylene group of middle of imipramine is responsible for the dissimilar stereochemical properties and prevents conjugation among the rings. Secondary metabolite (desipramine) of imipramine is similar to imipramine as an antidepressant while it is also showing some dissimilarity from imipramine. It might be possible that desipramine responsible for therapeutic responses to imipramine but it is no more effective or rapidly acting than imipramine [75].

7.2 Monoamine oxidase inhibitors

Among the all clinically introduced drugs, monoamine oxidase inhibitors were found to be first drugs for the treatment of depression while these are replaced by tricyclic and other types of antidepressant drugs because these having more efficacies and less side effects than the monoamine oxidase inhibitors. Phenelzine, tranylcypromine and iproniazide are the example of monoamine oxidase inhibitors. That drug irreversibly inhibits the MAO-A and MAO-B enzymes [76].

7.3 Selective 5-hydroxytryptamine reuptake inhibitors

These drugs also called as selective serotonin reuptake inhibitors or SSRIs, including flouxetine, fluvoxamine, paroxetine, citalopram and sertraline. SSRIs are most commonly prescribed for the treatment of depression. These are showing selectivity for the 5-HT not for noradrenaline uptake. SSRIs produced less anticholinergic side effects than the tricyclic antidepressant drugs. They are equally effective as MAOIs and TCAs for treating the depression but in case of severe depression, less effective than TCAs [76].

7.4 Sites of action of antidepressant drugs

Diagram is showing noradrenergic (top) and serotonergic (bottom) nerve terminals. Sevsral types of drugs such as SSRIs, SNRIs and TCAs increase the availability of noradrenergic or serotonergic neurotransmitters at synaptic cleft by blocking the transporter of norepinephrine and serotonin neurotransmitter at presynaptic terminals. MAOIs used for the inhibition of catabolism of norepinephrine and serotonin. Some antidepressant drugs like trazodone has direct effects on serotonergic receptors. Antidepressant drugs are used for the treatment of chronic depression, desensitizes presynaptic autoreceptors and heteroreceptors. These are responsible for producing long lasting changes in monoaminergic neurotransmission. Effect of antidepressant drug on postsynaptic receptors, including modulation of GPCR signaling and activation of protein kinase & ion channel (See Figure 1) [75].

Figure 1.

Modulation of GPCR signaling and activation of protein kinase & ion channel.

8. Conclusion

Different types of psychiatric problems, particularly sadness, depression and anxiety are afflicting an increasing number of people. These mental diseases not only have a negative impact on people’s daily lives, but they also place a significant financial burden on society. The psychopharmacology of herbs has gotten a lot of attention in recent decades. Finally, it may be concluded that, Achyrantes aspera extract exert a protective effect against physically induced depression. It has been also proved that herbal drugs show lesser adverse effects as compared to synthetic drugs that’s why Achyranthes aspera may be used for the treatment of depression as an herbal remedy.