|Year : 2022 | Volume
| Issue : 1 | Page : 3-10
Critical note on pretreatment (Shodhana) of Bakuchi (Psoralea corylifolia L.)
Sarika Makwana, Nikhil Mehere, Prashant Bedarkar, Patgiri Biswajyoti
Department of Rasa Shastra & Bhaisajya Kalpana, I.P.G.T. & R.A., Gujarat Ayurved University, Jamnagar, Gujarat, India
|Date of Submission||01-Oct-2021|
|Date of Decision||14-Feb-2022|
|Date of Acceptance||14-Feb-2022|
|Date of Web Publication||07-Jul-2022|
Dr. Sarika Makwana
Department of Rasa Shastra & Bhaisajya Kalpana, I.P.G.T. & R.A., Gujarat Ayurved University, Jamnagar 361008, Gujarat
Source of Support: None, Conflict of Interest: None
Bakuchi (Psoralea corylifolia L.) is an herb mainly indicated for the treatment of skin diseases in the classical text of Ayurveda. Before the use of several potent herbs, metals, minerals, and poisonous plants, specific processing is mentioned to be done to minimize the untoward effect of the drug or to make the drug more suitable for further processing as mentioned in Ayurveda classics. Such procedures are considered pretreatment (Shodhana). Although classical texts of Ayurveda have mentioned pretreatment of Bakuchi fruits before their therapeutic use, its internal administration after processing is not prevalent in clinical practice. This pretreatment may be considered as the Shodhana procedure of Bakuchi. Accordingly, data were assembled in the context of pretreatment of Bakuchi from Ashtanga Samgraha, Gadanigraha, Rasoudhhara Tantra, Vrunda Madhava, Anandakanda, Rasakamadhenu, and from published researches. Three procedures, viz. Nimajjana (immersion), Prakshalana (washing with water), and Bharjana (roasting), were mentioned for pretreatment of Bakuchi. Pretreatments are noted as soaking of Bakuchi fruits in Gomutra (cow’s urine) or Ardraka Swarasa (juice of Zingiber officinale Rosc.) for 7 or 21 days or Bibhitaka Kwatha (decoction of Terminalia belerica Roxb.) for 1 night and Bharjana (roasting) in Ghee. Blisters occur because of the presence of furanocoumarins like psoralen in formulations, which holds Bakuchi. Pretreatment performed on Bakuchi fruits may derive newer chemical moieties, further rendering it helpful to minimize adverse drug reactions, increase the efficacy of Bakuchi or its containing formulation, and further break the pathogenesis of the disease.
Keywords: Bakuchi, pretreatment, Psoralea corylifolia L, Shodhana
|How to cite this article:|
Makwana S, Mehere N, Bedarkar P, Biswajyoti P. Critical note on pretreatment (Shodhana) of Bakuchi (Psoralea corylifolia L.). J Drug Res Ayurvedic Sci 2022;7:3-10
|How to cite this URL:|
Makwana S, Mehere N, Bedarkar P, Biswajyoti P. Critical note on pretreatment (Shodhana) of Bakuchi (Psoralea corylifolia L.). J Drug Res Ayurvedic Sci [serial online] 2022 [cited 2022 Aug 15];7:3-10. Available from: http://www.jdrasccras.com/text.asp?2022/7/1/3/350055
| Introduction|| |
Bakuchi (Psoralea corylifolia L.), a pharmacopoeial classical drug being extensively used in Kushtha (skin diseases) and Shvitra (vitiligo), possesses an evident greater therapeutic utility in many skin diseases as well. Though Bakuchi has been used since ages in Ayurvedic therapeutics, its internal administration after processing (Shodhana) is not prevalent in clinical practice. The specific processing is mentioned to be done in several potent herbs, metals, minerals, and poisonous plants before their use in Ayurveda classics. It is purposed to minimize the untoward effect of the drug or to make the drug more suitable for further processing. Such procedures are considered pretreatment or Shodhana. This procedure is done to reduce and or eliminate harmful/ undesirable pharmacological effects of the drug, for change in pharmacological properties, the addition of newer pharmacological properties, regulation in the potency of pharmacological properties, or therapeutic effects. Ayurveda classics described different principles for pretreatment of Bakuchi in various formulations, which may be considered as Shodhana.
According to Ayurveda classics, Sphota (blisters) may occur during the treatment of Bakuchi, which is indicated for vitiligo and it may be considered as a phenomenon and positive sign in the management of vitiligo., Probable adverse effects for a higher dose of Bakuchi are mentioned as Chhardi (vomiting), Shirahshoola (headache), Avasada (depression), Virechana (diarrhea), and Hrillasa (nausea). Gastrointestinal discomfort due to internal administration of Bakuchi Churna is also reported in one case study. The corrosive action of Bakuchi is due to one of its chemically active constituents Psoralen present in the fruits., Short-term side effects of Psoralens are nausea, vomiting, erythema, pruritus, xerosis, and skin pain due to phototoxic damage of the dermal nerve and may cause cutaneous and genital skin malignancies. On the contrary, they are delineated for multiple therapeutic attributes too like management of vitiligo and immunosuppression. Hence, pretreatment by various media with different principles performed on Bakuchi may minimize the probable adverse drug reactions and increase the efficacy of Bakuchi or its containing formulations. As per this vision, this study is designed to compile all the relevant classical references and work done on the pretreatment of Bakuchi with regard to its method of pretreatment and its principle. Further, it has been interpreted based on various media for pretreatment, advantages, and its therapeutic arena as per classical indications.
| Materials and Methods|| |
Samhita, Chikitsa Grantha, Rasa Grantha, and Nighantu were referred using the words Bakuchi, “synonyms of Bakuchi” with and without predetermined phrases related to common Ayurvedic pharmaceutical procedures (Samskara) (in Samskrit language and language of commentary) and Bakuchi Shodhana, Shuddha Bakuchi, and Shodhita Bakuchi for collection of depictions on pretreatment of Bakuchi. Total 9 Samhita, 18 Chikitsa Grantha, 32 Rasa Grantha, and 26 Nighantu were referred critically to search evidence for pretreatment on Bakuchi. Components of search or review included in this study were pretreatment of Bakuchi considered method of pretreatment, recommended dose, Sahapana or Anupana (vehicle), and indications from Ayurvedic classical texts.
Information on pretreatment of Bakuchi was mentioned in eight classical texts Ashtanga Samgraha, Gadanigraha, Rasoudhhara Tantra, Vrunda Madhava, Rasakamdhenu, and Anandakanda. The available data have been systemically classified and presented in tabular form with regard to their particulars [Table 1].
|Table 1: Depiction of pretreatment of Bakuchi (Shodhana) in Ayurveda classics|
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Pretreatment of Bakuchi is illustrated in classics such as Ashtanga Samgraha, Gadanigraha, Rasoudhhara Tantra, Vrunda Madhava, Rasakamdhenu, and Anandakanda.
According to the procedure of pretreatment, three categories of pharmaceutical operations are noted, that are, Nimajjana (immersion), Prakshalana (washing with water), and Bharjana (roasting). Different durations for pretreatment of Bakuchi are observed for Nimajjana, that are, 7 or 21 days, and 1 night. Nimajjana procedure is mentioned by soaking Bakuchi fruits in cow’s urine (7 or 21 days), Ardraka Swarasa (7 days) (juice of Zingiber officinale Rosc.), and Bibhitaka Kwatha (1 night) (decoction of Terminalia belerica Roxb.) liquid media. Bharjana procedure is mentioned in Ghee media by Ashtanga Samgraha. Maximum references for the Nimajjana process were found. After the collection of Bakuchi fruits in Pushya Nakshatra, Prakshalana by water (washing) is also mentioned in the Anandakanda classics.
In a textbook of Drvayaguna Vigyanam, Shodhana for Bakuchi fruits described as Nimajjana in Adraka Swarasa (ginger juice, Z. officinale L.), cow’s urine media. Cow’s urine, Dhatriphala Rasa (juice of Indian gooseberry, Emblica officinalis Gaertn.), and Vijayasara (Pterocarpus marsupium) Tvaka Kwatha are mentioned as Anupana and lukewarm water and Laghu panchamoola Siddha Peya as Sahapana.
Ashtanga Sangrahakara has mentioned lukewarm water as Anupana of roasted Bakuchi fruits in Ghee. Roasted powder of Bakuchi is administered with Anupana of Laghu Panchamoola Siddha Peya after complete digestion. Maximum therapeutic dose is mentioned in Ashtanga Samgraha as 1 Karsha (12 g) in the form of Bakuchi Kalpa. Shvitra is found as a common indication among all reviewed references for the therapeutic indication of Bakuchi. Ghrita Bhrishta Bakuchi is indicated for Gulma (abdominal tumor) [Table 1].
Chhaya Sushka (drying in shade) has been specified in many references as pretreatment of Bakuchi as well as after completion of pretreatment (Nimajjana) of Bakuchi except only one reference for Atapa Shoshana (drying in sunlight), which is mentioned separately without any other pretreatment like Nimajjana. Upon review, in none of the references of Nimajjana as pretreatment of Bakuchi, the process of Nimajana is mentioned to be carried out in sunlight [Table 1].
| Discussion|| |
The Samskara which achieves transformation of inherent attributes are carried out by pharmaceutical operations involving the use of liquid media for processing (water), heating, cleaning, maceration, region of origin, growing or collection, Kala (season and or time of collection, maturation, and aging), Patra Samyoga (storage, placing in certain vessel or packaging), flavor, and Bhavana (levigation/trituration). The raw drug undergoes certain processing (principle for Shodhana) known as Samskara which can bring out an alteration in the natural qualities and properties of raw drugs. Accordingly, pretreatment on Bakuchi has been emphasized by Ayurveda seers in classics. Bakuchi has been used since ages in Ayurvedic therapeutics but its internal administration after pretreatment is not prevalent in clinical practice. Nimajjana, Bharjana, and Prakshalana principles are specified for the pretreatment of Bakuchi. Cow’s urine, Bibhitaki Kwatha, Ardraka Swarasa, and Ghee media are used for the pretreatment with various pretreatment duration (7 or 21 days and 1 night). The media and principle used in the process of pretreatment have been intended to either break down, destroy, reduce, or transformation of chemical constituents that do not have a desirable therapeutic effect or are potential for toxicity.
Blister formation, inflammation, angioedema, and skin thickening and burning sensation are noticed in published research on Bakuchi containing formulations as constituents of Bakuchi showed photosensitivity and dermatological reactions., Formation of blisters may not be expected as part of the management of vitiligo, although it is mentioned in Ayurveda classics as a normal phenomenon with the administration of Bakuchi. However, the occurrence of blisters is not expected with formulations of Bakuchi where it is not specified for dermatological reactions. Hence, blister formation and any other dermatological reactions in such patients treated with formulations of Bakuchi may be an adverse drug reaction. To overcome these adverse effects, pretreatment may be mandatorily specified for Bakuchi or its containing formulations before their use in respected formulations. Many chemical changes have been documented on its secondary products during the pretreatment according to its treatment principles and various media. Hence, their adverse reactions may be reduced and not expected for their respective formulation where pretreatment of Bakuchi is mentioned in the classics.
The principles of the Nimajjana method may be correlated to the reaction that happens between the solid material (Bakuchi fruits) and the liquid media (Shodhana media). According to the concentration gradient, the normal osmosis process occurs between a solid material and liquid media. When liquid enters in solid material, it swells up. The process employed for 7 or 21 days will enhance the osmosis and additional chemical reactions in it. Solution of the soluble components takes place within the cells, then there is the escape of dissolved material through the solvent boundary layer by the process of diffusion and finally separation of the solution from the drug occurs.Nimajjana process in cow urine may be alike to alkaline hydrolysis. The action of alkali on 8-hydroxy-psoralen takes place in one stage and then leads to opening of the pyrone ring and formation of a salt of coumarinic acid., The lactone ring in furocoumarins is susceptible to alkaline hydrolysis. This may further lead to modification in chemical compounds of Bakuchi fruits.
Ayurvedic classics mentioned pretreatment of Bakuchi fruits in the form of immersion for 1 night in Bibhitaki Kwatha as well. In the context of Samskara, Toya Sannikarsha is taking place during this pretreatment of Bakuchi. This process may be identical to the hydrolysis process (breakdown of chemical constituents to derive newer chemical constituents upon treatment with water). Two benzofuran glycosides, namely psoralenoside and isopsoralenoside, from the fruits can be easily converted into psoralen and isopsoralen on hydrolysis. Thus, these alkaloids are interconvertible through the process of hydrolysis.
During Nimajjana, the most prevalent chemical changes may occur as hydrolysis in the case of Bakuchi. Cyclic changes that are conversion of furanocoumarin to coumarinic acid and from benzofuran to furanocoumarin compounds may lead to various pharmacological compounds. Thus, processed Bakuchi may contain newer pharmacological active molecules as that of unprocessed Bakuchi. These cyclic reactions are taking place in different media such as cow’s urine, Bibhitaki Kwatha, and Ardraka Swarasa with diverse chemical attributes in terms of phytochemical constituents and are proven as biologically active media [Figure 2].
Secondary metabolites of furanocoumarins may be unstable and degraded by light further reducing their effectiveness. Even cow urine is reported to undergo a series of chemical interactions after photo-activation where few biogenic volatile organic and inorganic compounds such as CO2, NH3, CH4, methanol, propanol, and acetone, and metabolic nitrogenous products may be formed. These altered chemical constituents of cow urine after photoactivation (by sunlight) may interact with degraded constituents of psoralen, further raising concerns on derived product standardization, safety as well as efficacy. The reason for the same may be psoralen photosensitization possesses to altered cytokine secretion, including an increase in the expression of interleukins-1, 6, and 10 as well as immunosuppressive prostaglandins. Owing to these reasons ancient seers might have purposefully mentioned avoiding sunlight exposure for Nimajjana as well as drying after Nimajjana.
During the Bharjana process of Bakuchi fruits, fats in fruits (containing lipoidal pharmacologically active phytoconstituents) undergo lipid peroxidation. This process further may generate newer fatty acid complexes with phytoconstituents of Bakuchi fruits especially lipoidal (constituents of fruit oil). Fatty acids are unstable and more susceptible to chemical reactions. Pharmacological activities of alkaloids that are present in the fruit have good lipophilicity. That is comparatively nonpolar and likely soluble in Ghee. Lipophilic furanocoumarins are selectively bound to these lipid-rich media (Ghee). These lipophilic interactions may play important roles in contributing to the biological actions of these compounds. This may show a propensity of furanocoumarins to bind and interact with biological membranes in intact tissue [Figure 2].
Coumarinic acid, which is secondary product of 8-hydroxy-psoralen, may be derived from alkaline hydrolysis (Nimajjana in cow urine). It has been reported for antioxidant activities in reducing oxidative stress and inflammatory reaction. Published studies support the efficient transdermal delivery, efficacy in subsequent skin pigmentation, and reducing skin erythema due to ultraviolet radiation exposure., Target prediction of coumarinic acid is confirmed on carbonic anhydrase I, II through Swiss target prediction analysis conducted in post-review phase in this study (Swiss target prediction database). Carbonic anhydrase I, II are zinc-containing enzymes and Zn has a pivotal role in melanogenesis., It is to maintain intracellular homeostasis and restore physiological pH after the release of acid to the resorption site, alkaline products created during the acidification process have to be disposed of with the help of bicarbonate/chloride exchangers. Coumarinic acid is an amphiphilic compound that attains both hydrophobic and hydrophilic properties at neutral pH. Water solubility of coumarinic acid (4.22e–03 mol/L) is more than psoralen (1.85e–03 mol/L) and iso-psoralen (1.02e–03 mol/l) compounds. 0.85 bioavailability score of coumarinic acid showed through Swiss absorption, distribution, metabolism, and excretion. This observed value is more than the bioavailability score of psoralen (0.55) and isopsoralen (0.55). Zinc is one of the trace elements that play an important role in the process of melanogenesis. Pathogenesis of vitiligo is oxidative stress leading to the destruction of melanocytes. Accordingly, zinc, coumarinic acid can control vitiligo by inhibiting the production of free radicals. An increase in solubility and bioavailability score of secondary products of furanocoumarins may possess alteration in potency through newly derived chemical moieties [Figure 1].
|Figure 1: Mechanism of pretreatment of Bakuchi and its activity on therapeutic indications|
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Psoralen and isopsoralen have shown target prediction on nuclear factor NF-kappa-B p105 and Acetylcholinesterase. NF-kappa-B p105 (NF-κB) is an ancient protein transcription factor and is considered a regulator of innate immunity and mediator of inflammatory processes. Acetylcholinesterase (AChE) may be playing important role in the pathogenesis of vitiligo. In patients with vitiligo, a decrease in acetylcholine esterase and inactivate due to high oxidative stress are reported. During the Bharjana process, derived chemical moieties may show sustained release metabolic nature owing to their deposition in lipoidal tissues, fatty tissues in the body like subcutaneous fat, showing the effect on skin appendages (dermis, epidermis). Thus, it may be helpful on indications of Bharjita Bakuchi powder, that is, efficacy in the management of Gulma. Ghee possesses Samskara Anuvartana property, which suggests that it imbibes attributes of drug easily other than other media with which it is being treated pharmaceutically [Figure 1].
Cow urine possesses a Rasayana activity, which is responsible for modulation of the immune system and also acts as a bio enhancer. It has been reported to be a potent immunomodulator that increases both humoral and cell-mediated immunity. The role of autoimmunity and oxidative stress are well known in the pathogenesis of vitiligo. Research showed a deficiency of antioxidant substances in vitiliginous skin. Zinc in combination with other micronutrients such as copper, cobalt, nickel, iron, manganese, and calcium attenuates an important role in the process of melanogenesis. Cow’s urine contains phenolic acids such as gallic, caffeic, ferulic, coumaric, cinnamic, and salicylic acids. It is a major source of trace elements. Trace elements may interact with products of hydrolysis to form newer organo-inorganic complexes. There are fair chances of formation of many complexes of contents of Bakuchi, products of hydrolysis of its constituents with each other which may lead to change in therapeutic attributes of Bakuchi after immersion treatment.
Bibhitaki holds biological active compounds such as gallic acid, bellaricanin, lignins, and ellagic acid make highly potent antioxidants, which may be responsible for its immunomodulatory activity. Its extract neutralizes reactive oxygen species (ROS) and scavenges free radicals., Gallic acid is reported as an active component responsible for stimulation of the immune system of mice, whereas it reduced the production of IFN-a and IL-2. Gallic acid plays an important role in redox homeostasis and increases the gene expression of antioxidant enzymes.The fruit extract is reported to be astringent, antioxidant, antiemetic, anti-inflammatory, and anthelmintic activities. The addition of bioactive contents and secondary products in Bakuchi through the hydrolysis process may be helpful to overcome the pathogenesis of the indicated disease [Figure 2].
Zingiber officinale Roscoe reported bioactive components such as volatile oil, gingerol, shogaol, and zingerone compounds. The antioxidative properties of ginger and its components have been reported in various in vitro and in vivo tests [Figure 2]. 6-Shogaol has shown the most potent antioxidant and anti-inflammatory properties in ginger, which can be attributed to the presence of alpha, beta-unsaturated ketone moiety. Skin is a major target of oxidative stress. Evidence suggests that oxidative stress is the cause of melanocyte disappearance in vitiligo. 6-SG has the potential for use as an antioxidant agent in the prevention and treatment of vitiligo or other oxidative stress-associated pigmentary disorders. Thus, it is evident that the media used for pre-treatment may alter the therapeutic efficacy.
Subchronic toxicity study (60 days) of Gomutra Shodhita Bakuchi powder suggested that it is devoid of any serious toxic effects or adverse effects in rats even at higher dose level (TED––adult human dose: 0.27 g/d, TED 5: 1.3 g/kg and TED 10: 2.7 g/kg) on repeated administration in animals. In subchronic toxicity; the drug was capable of affecting the liver, kidney, and stomach at higher doses. Other parameters that increased or decreased were found within in physiological range. Therefore, Gomutra Shodhita Bakuchi powder may be classified as safe based on subchronic toxicity study.
All the aforementioned supportive references revealed that either Shodhana media and process of Shodhana and or derivatives of the process of Shodhana brings about changes in phytoconstituents of Bakuchi which are responsible to counteract possible side effects of Bakuchi, its safety, efficacy, and widening its therapeutic arena as well. References also support the immunomodulatory activity, anti-oxidant activity of Shodhana media, which may further helpful to break the pathogenesis of disease and support to increment in the therapeutic efficacy of the drug. Nimajjana and Bharjana process may give alteration in chemical moieties and derive newer pharmacological active molecules. This may be helpful through its biological activities for vitiligo disease to arrest and or revert its pathogenesis. If Shodhita Bakuchi is found to have upper hand in terms of pharmacological or Rasayana properties as that of unprocessed Bakuchi fruits, possible changes in Shodhana in terms of generation of newer phytochemical moieties may be further preliminarily explored with insilico-models such as target prediction, molecular docking of newly formed phytoconstituents followed by in vitro and in vivo studies. The review reveals that pretreatment of Bakuchi fruits is specifically mentioned for long-term therapeutic indications such as skin disorders, Shvitra and Rasayana.
| Conclusion|| |
Pretreatment of Bakuchi is proposed in the classical text to improve its therapeutic utility as well as to restrict the untoward effects. Pretreatment of Bakuchi in cow urine can be preferred when it is to be used in the treatment of skin diseases, vitiligo, and for Rasayana purposes. Similarly, pretreatment by roasting with Ghee can be done for Bakuchi intervention to manage Gulma (abdominal tumor) disease. Nimajjana in Bibhitaki Kwatha may be intended for treating vitiligo. Further research work on the pre-clinical and clinical ground with Bakuchi pretreatment in specific media is needed to explore and validate the aforementioned claims.
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[Figure 1], [Figure 2]