AYU (An International Quarterly Journal of Research in Ayurveda)

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 42  |  Issue : 1  |  Page : 19--29

Efficacy of external application of oil and gel dosage forms of Aragvadhadi formulation in combination with Rasayana Churna in the management of Shwitra (vitiligo) - An open-labeled comparative clinical trial


Sarika Makwana, Dipali Parekh, Prashant Bedarkar, Biswajyoti Patgiri 
 Department of Rasa Shastra and Bhaisajya Kalpana, ITRA, Gujarat Ayurved University, Jamnagar, Gujarat, India

Correspondence Address:
Sarika Makwana
Department of Rasa Shastra and Bhaisajya Kalpana, I.P.G.T. and R.A. Gujarat Ayurved University, Jamnagar - 361 008, Gujarat
India

Abstract

Introduction: Aragvadhadi Taila (ART) is one of the herbomineral formulations mentioned in Chakradatta indicated in Shwitra (vitiligo). Modification of Taila form into gel form reduces the risk of contamination in view of arsenical contents (Manahshila, Haratala) assures precise dose administration at desired site (by avoiding spreading). The gel is a comparatively acceptable dosage form than that of medicated oil. Aim: The aim of the study is to evaluate the comparative efficacy of Aragvadhadi formulation in Taila (ART: Aragvadhadi Taila) and gel (ARG: Aragvadhadi gel) dosage forms with the internal administration of Rasayana Churna in the management of Shwitra. Materials and methods: The study was a randomized open labeled, involving 66 patients of Shwitra that were randomly divided into two groups. Patients registered in group A (n = 34) were treated with local applications of ART and group B (n = 32) with ARG for 2 months. Rasayana Churna (3 g), along with the equal quantity of honey and Ghrita was given twice a day after the meal in both groups. Wilcoxon signed-rank test was applied to evaluate the effect of therapy in the individual group for subjective criteria like vitiligo area scoring index score, size and number of patches, Rukshata (dryness), Saparidaha (burning sensation), Bahalatva (thickening), Kandu (itching) while the comparison of results between the groups for the same by applying Coefficient of Variation (CV). Results: Group B showed better and consistent results in all signs and symptoms except Rukshata, Saparidaha in terms of Coefficient of Variation. In both the groups, statistically highly significant improvement was found in signs and symptoms of Shwitra such as Saparidaha, Kandu, size of patches and number of patches; however, the difference between the groups was statistically insignificant. Conclusion: Both the forms (ART, ARG) of Aragvadhadi formulation along with Rasayana Churna were found as a safe and effective treatment in vitiligo with significant pigment regeneration capacity as topical use for application over 2 months.



How to cite this article:
Makwana S, Parekh D, Bedarkar P, Patgiri B. Efficacy of external application of oil and gel dosage forms of Aragvadhadi formulation in combination with Rasayana Churna in the management of Shwitra (vitiligo) - An open-labeled comparative clinical trial.AYU 2021;42:19-29


How to cite this URL:
Makwana S, Parekh D, Bedarkar P, Patgiri B. Efficacy of external application of oil and gel dosage forms of Aragvadhadi formulation in combination with Rasayana Churna in the management of Shwitra (vitiligo) - An open-labeled comparative clinical trial. AYU [serial online] 2021 [cited 2023 Feb 8 ];42:19-29
Available from: https://www.ayujournal.org/text.asp?2021/42/1/19/362929


Full Text



 Introduction



In Ayurveda, Shwitra has been listed to be the worst among Kushtha that causes ugly appearance of the body. Acharya Vagbhatta has described Shwitra as more dangerous than Kushtha as it's prognosis worsens with duration as it becomes incurable (Asadhya) very quickly.,[1] Vitiligo is an acquired skin disorder caused by the disappearance of pigment cells from the epidermis that gives rise to well-defined white patches, which are often symmetrically distributed. It can be cosmetically disfiguring and it is a stigmatizing condition, leading to serious psychological problems in daily life. In India, Gujarat is considered to have the highest incidence in the world, with 8.8% of people affected by vitiligo.[2]

The modern medical system has treatment modalities, including narrow-band ultraviolet B (311 nm) therapy, transplantation of autologous pigment cells, and thin split-thickness skin graft in various modalities.[3] According to a survey, these treatment modalities have limited use because of adverse events such as pruritis (37%), erythema (>grade 2, 22%), nausea (20%), and headache (8%).[4] Therefore, it is the need of time to look for treatment with less adverse events as well as more effective treatment from Ayurveda.[5]

Aragvadhadi Taila (ART) is one of the compound formulations mentioned in Chakradatta indicated in Shwitra (vitiligo).[6] This herbomineral formulation consists of two arsenicals, i.e., Shuddha Manahshila (processed realgar), Shuddha Haratala (processed orpiment). Aragvadha is considered Kushthagna Dravya in Aragvadhiya chapter in place of Adhyaya in text Charaka Samhita.[7] Acharya Sushruta has mentioned Aragvdhadi Gana which is separately used to cure skin diseases (Kushtha).[8] Acharya has advocated Aragvadha as external and internal remedies for skin diseases and injury, etc. Rasaratna Samuchhya has mentioned Kushthahara property of processed Haratala.[9] However, there is no published research work on modification of this formulation. Modification of Taila form into gel reduces the risk of contamination in view of arsenicals content (Manahshila, Haratala) assures precise dose administration at desired site (by avoiding spreading). Disadvantages of topical medicament oil are unwanted spreading, chances of irritation, hyperpigmentation of healthy skin, and inconvenience in public transport. Gel is a comparatively convenient dosage form than that of medicated oil.

Vitiligo may cause emotional, psychological consequences. Rasayana Churna containing Guduchi (Tinospora cordifolia Linn.), Amalaki (Emblica officinalis Linn.), and Gokshura (Tribulus terrestris Linn. in equal proportion has rejuvenation properties.[10] Therefore, Rasayana Churna has been selected in the study.

Consequently, the study is undertaken to evaluate the comparative clinical efficacy of Aragvadhadi Taila and its gel form along with Rasayana Churna in Shwitra (vitiligo).

 Materials and method



The study was a randomized open labeled, involving 66 patients with vitiligo fulfilling the inclusion criteria. Each patient was examined in detail. Relevant pathological (total leukocyte count, differential leukocyte count, haemoglobin erythrocyte sedimentation rate, total red blood cells, absolute eosinophil count, and urine examinationand biochemical investigations (post prandial blood sugar, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphates, Sr creatinine, and blood urea) were done before and after treatment to assess the disease condition and to exclude any other pathology. Informed consent was obtained from all the patients before including in the trial. The study was also approved by Institutional Ethics Committee clearance (7/-A/ETHICS/2017-18/2093, dated: 23/11/2017) and registered at the clinical trial registry of India, ICMR, New Delhi, vide CTRI/2018/01/011120 dated 03/01/2018.

Inclusion criteria

Patients having classical signs and symptoms of Shwitra such as Arunata (vermilion colored), Mandala (circular), Rukshata (dryness), Paridhvanshi (when rubbed scales off morbid skin) for Vatika Shwitra; Padmapatra Pratikasam (eruptions resembling the petals of a lotus flower), Sadaha (burning sensation), Romavidhvanshi (loss of hairs), Tamra (coppery colored) for Paitika Shwitra and Kandu (itching), Shweta (white colored), Bahala (thick) and Snigdha (glossy) for Shleshmika type of Shwitra were included in the study. Patients in the age group between 16 and 60 years irrespective of sex and chronicity of <10 years were included.

Exclusion criteria

Patients having chronicity >10 years, patients of cardiac, renal, hepatic diseases, other conditions such as insulin-dependent diabetes mellitus (IDDM), non-IDDM, gravid and lactating women, women in fertile age planning for conception within the next 3 months. Patients of patches due to burning or chemical explosion, lesions at Guhyanga (genital organ), Panipadatala (sole of palm and feet), Oshtha (lips), Sarvanga (generalized lesion over the body), and patches with Raktaroma (reddish hair) and Samsakta (coalescent) were excluded.[11],[12]

Method of preparation of the trial drugs

Aragvadhadi Taila (ART) was prepared as per reference of Chakradatta in compliance with classical guidelines, in 5 batches of 2 lit. each at the institutional Bhaishajya Kalpana laboratory. Aragvadhadi Taila contains Sarshapa Taila (mustard oil), Aragvadha fruit (Cassia fistula Linn.), Dhava (Anogeissus Latifolia Linn.) bark, Kushtha (Saussurea lappa C.B. Clarke), Haridra (Curcuma longa Linn.), Daruharidra (Berberis aristata DC), Shodhita Manahshila (Processed red arsenic sulfide), Shodhita Haratala (Processed yellow arsenic sulfide), and Gomutra (cow's urine). Pharmaceutical and analytical standardization were carried out for the ART.[13] Aragvadhadi gel (ARG) was prepared by adding 15% of Aerosil in Aragvadhadi Taila. Both the trial drugs were stored in airtight container.

Material

Of the 66 registered patients in group A (n = 34), patients of Shwitra were treated with external application of ART and internal administration of Rasayana Churna[14] 3 g with Sahapana (vehicle) of honey and Ghrita 2 times/day, and in group B (n = 32), Aragvadhadi gel (ARG) Q. S. for external application and Rasayana Churna for internal administration.

Posology

In group A, patients were treated with external application of ART and internal administration of Rasayana Churna 3 g with Sahapana of Madhu and Ghrita with equal quantity after meal 2 times/day and in group B were treated with ARG Q. S. for external application and Rasayana Churna for internal administration after the meal. The quantity sufficient drug was advised to apply locally over patches in the morning with exposure to sunlight for 30 min for 2 months. Follow-up was taken at weekly intervals for VASI (Vitiligo Area Scoring Index) score, signs and symptoms and probable ADRs for 1 month. Other medicines were stopped, and dietary restrictions were advised in both the groups as stated in classics.[15]

Wholesome diet

Patients were advised to take in diet such as old rice (Puranashali), wheat (Godhuma), green gram (Mudga), light food (Laghuahara), and Patola (bitter gourd), old cereals, seasonal fruits, green vegetables such as Methika (Trigonella foenum-graecum Linn.), Patola (Trichosanthes dioica Roxb.), and Amalaki (Phyllanthus emblica Linn.).

Unwholesome diet

Viruddhahara (incompatible food), Guru Ahara (heavy food), Vidahi Ahara (spicy, pungent food), Vishtambhi Ahara (constipatives), Anupamamsa (sea food), Kanda-Moola (roots and tubers), Amla–Katu-Lavana Rasa (sour, pungent, salty food), curd, fish, canned food, junk foods, milk and milk products, oily and fermented food products, consumption of food at inappropriate time, late, and day sleep were advised to avoid.

Criteria for assessment

Special vitiligo area scoring index (VASI)[16] scoring pattern was adopted for evaluation of the status of affected area. The score was given based on size and number of patches, percentage of body area involvement, and chronicity of patches. For the assessment of the involvement of body surface area, the rule of nine[17] used to calculate the percentage of burn was considered with certain modifications. The whole body was allocated in scores, but looking into the nature of the disease, score was further specified regions to the organs. Subjective criteria involve Rukshata (dryness of the skin), Saparidaha (burning sensation), Kandu (itching), and Bahalatva (thickening of the skin) were assessed before and after the treatment [Table 1], [Table 2], [Table 3].{Table 1}{Table 2}{Table 3}

Overall effect of therapy

Complete remission: 100% improvement in subjective and objective parametersMarked improvement: >75%–99% in subjective and objective parametersModerate improvement: >50%–75% in subjective and objective parametersMild improvement: >25%–50% in subjective and objective parametersUnchanged: Up to 25% improvement in subjective and objective parameters.

Statistical analysis

The percentage of improvement in each parameter in all the treated groups was calculated. Wilcoxon signed-rank test was applied to evaluate the effect of therapy in the individual group for subjective criteria such as VASI score, size, and number of patches, Rukshata (dryness), Saparidaha (burning sensation), Bahalatva (thickening), Kandu (itching) while the comparison of results between the groups in subjective criteria was done by applying coefficient of variation (CV). The overall effect of therapy on each scale was calculated with reference to percentage improvement in all symptoms. Finally, the overall effect of therapy was evaluated by enumerating the number of patients in improvement categories.

 Observations and Results



In the present clinical study, a total of 80 patients were assessed for eligibility. Among them, 72 patients were registered, i.e., 35 in group A and 37 in group B. Thirty-four patients in group A and 32 patients in group B had completed the treatment. One patient in group A and five patients in group B left the treatment in between. In group A, one patient refused to continue medicine. In group B, from three patients were resided much far from Jamnagar city and could not came regularly, one patient was migrated to another city for further study purposes, and 1 discontinued without any reason [Chart 1]. Detailed demographic data are introduced in [Table 4]. There is no statistically significant difference (P > 0.05) in the effect of therapies in group A and B on biochemical parameters such as FBS, S. cholesterol, S. triglyceride, and hematological parameters like Hb%, ESR., TLC., neutrophils, lymphocytes, eosinophils, and monocytes. All changes were within normal biological ranges.[INLINE:1]{Table 4}

Comparison of effect of treatment within same group (paired 't' test) showed that ART treated group A exhibited highly significant improvement in burning sensation (45.9%, P < 0.0001) and ART gel treated group B showed highly significant reduction in size of patches (45.94%, < 0.001), number of patches (34.25%, P < 0.001), VASI Score (52%, P < 0.0001), itching (17.99%, P < 0.001) and significant reduction in thickening of skin (43.33%, P < 0.0038). Upon comparison of effect of treatments among groups, group A exhibited better result in dryness, burning sensation whereas group B in VASI score, number of patches, thickening of skin and itching. There was statistically insignificant difference (unpaired 't' test) (P > 0.999) in effect of treatment in between two groups on parameters VASI score, size of patches, number of patches, burning sensation, thickening and itching of skin whereas significant difference was noted in reduction in dryness in between groups. [Table 5].{Table 5}

Upon consideration of overall effect of treatment, ART (group A) showed mild improvement in 46.87%, moderate improvement in 43.75%, and marked improvement in 3.12% of patients. While, in 6.25% of the patients remained unchanged. ART gel (group B) showed mild improvement in 32.35%, moderate improvement in 52.94%, and marked improvement in 11.76% of patients Whereas merely 2.94% of the patients remained unchanged. None of the patients showed complete remission in either groups. [Table 6] and [Chart 2]{Table 6}[INLINE:2]

On applying coefficient of variation (CV), group B showed better and consistent results in all parameters except dryness, burning sensation. The major difference was found in the thickening of skin between comparisons of both the groups as that of other symptoms. It may be due to better localized action of the gel dosage form). [Table 7] {Table 7}

Photographs of acute and chronic patients from group A and B are presented in [Figure 1], [Figure 2], [Figure 3], and [Figure 4]. Patient suffered from blister formation depicted in [Figure 5], [Figure 6]. None of the patients reported complete cure with the treatment of 2 months duration. It was assesed in pilot study.{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}{Figure 6}

 Discussion



Psychological factors and incompatible food (salty and milk food together) are mentioned in classics as the prime causative factors for this disease. Acharya Charaka also stated that psychological factors may induce stress in the patients and become the triggering factor that triggers the disease manifestation mechanism.[18] 68.35% of patients had sour taste dominancy followed by sweet taste (55.69%) and salty taste (45.56%) in their diet. It revealed that Madhura (sweet), Amla (sour), and Lavana (salty) Rasa causes aggravation of Kaphadosha, Amla Rasa (sour taste) causes Rakta Dushti. Excessive taking of Amla, Lavana (salty taste), and Katu Rasa pungent taste causes vitiation of Pitta. Acharya Charaka has also mentioned these foods play an important role in the pathogenesis of Shwitra. About 65.82% of patients were observed in taking salty diet and milk while 21.51% were observed in taking sour food and milk together. These combinations food lead to vitiation of blood hence leads to Shwitra disease.[19] Acharya Charaka has mentioned the role of incompatible food in the manifestation of Shwitra.[20] This process plays an important role in the initiation of the pathogenesis of Shwitra. All these factors might have contributed to disturb the immunological balance of the body, thus causing autoimmune or process to paralyze the affected patient's melanocytes system to produce the lesions of vitiligo.[21]

In the present study, 35.44% of patients were reported in the age group of 18–25 years. Ayurvedic classics have stated Shwitra as the disease of dominant Pitta in Dosha triad. This is evident from the above data as Shwitra is more prevalent in the age group, which was Pitta Pradhana.[22] About 16.45% of patients were employee of brass industries. One cross-sectional descriptive research attributed to the use of raw materials, such as copper, in industries, which the workers grind and clean producing dust, which leads to black stain also over hands. Occupational dermatosis, i.e., vitiligo was found in 20 workers (1.9%), and a higher percentage of workers had found occupational dermatoses in this research.[23]

17.72% of patients had positive family history of disease. Among them, 11.39% of patients were having family history of vitiligo in 1st-degree relatives and 5.06% of patients had family history in 2nd-degree relatives. The occurrence of vitiligo is in the ratio of 1:3 when it comes to inheritance.[24] Comparatively less incidence of heredity in terms of % of the history of heredity (14%) in the present study and previous all thesis of the institute (mean 15.8 ± 0.98 of percent of patients with heridity) are suggestive of lower hereditary prevalence, which itself suggest that prevalence of locally adopted lifestyle could be a major player in increasing prevalence of nonhereditary vitiligo.[25] Familial occurrence has been reported to be in the range of 6.25% to 30% in many previous researches. 17.72% of patients had taken >1 h sun exposure time, and only 2.53% had taken excessive 4–5 h. Sun may affect highly reactive chemicals (called reactive oxygen species) in the skin that may play a role in triggering the disease in a genetically susceptible patients.[26] Normally, excessive sun exposure first causes skin reddening, followed by peeling of the outer skin layers and the formation of darker skin in the exposed area (tanned skin). However, in some cases, a reaction occurs in which the melanin production is blocked and the skin loses its color. The patches of white are usually at the site of the burn, but it is also possible for additional patches to begin appearing elsewhere.[27]

Prima facia results of therapy in all patients could be still very significantly better than those are acknowledged after analysis of the overall results of all patients within the group. Better results were observed in VASI score in patients with chronicity of 6 to10 years after follow-up period of 1 month, as compared to results on VASI score in same patients after treatment of drugs for 2 months which were insignificant in either group. It is suggestive that drug will not achieve a maximum therapeutic effect with 2 months of treatment and with more duration of treatment, there may be still better clinical efficacy and it may be recommended to increase the duration of treatment as well as follow-up in future studies so as to achieve still better results. Prima facia results of therapy in terms of overall reduction in VASI score in all patients could be still very significantly better than those are acknowledged after analysis of the overall results of all patients within the group. This is evident from very high increase in VASI score in patients of lesser (1–5 years) and less chronicity (<1 year) [Table 8]. Improvement in VASI score is reducing sequentially with increase in chronicity, but it is noteworthy that there is improvement in VASI score even in patients with chronicity of 6–10 years [Table 9].{Table 8}{Table 9}

Hence, fewer score in ARG suggests better management in Group B. This is evident from very high increase in VASI score in patients of lesser (1–5 years) and less chronicity (<1 year) [Table 8]. It could be recommended that a study should be conducted on chronic cases of vitiligo (more than 6 years chronicity) as there are poor clinical outcomes in such chronic cases with all possible treatment modalities with restrictions and along with treatment-related risks specifically in the younger population requiring long term management. Aragvadhadi Taila treated group showed more improvement in Rukshta parameter. As Rukshata may be dependent on treatment modality and it is likely a local or systemic response of the body or local skin to treatment, which may also be adverse effects of drug treatment (adverse drug effect-arsenicals).

Probable mode of action of the drug

Most of the ingredients in this Aargvadhadi Taila are Kushthaghna (indicated for skin diseases), Krimighna (anthelmintic), and Kandughna (pacifying itching) by virtue of dominancy of Rasadi Panchaka (pungent-bitter taste, Katu Vipaka [pungent postdigestive effect], Ushna Veerya [hot potency], and Sara-Tikshna Guna [mobile and sharp qualities]) and that acts on Bhrajaka Pitta (maintenance of normal skin color). Most of the drugs have Kapha Pittahara properties. Hence, Shwitra is Tridoshaja Pitta Pradhana Kushtha. Accordingly, this formulation might have helped in breaking the pathogenesis of Shwitra. Manahshila, Haratala, and Gomutra (cow's urine) are specially indicated for Shwitra.[28] Rasayana Churna is a polyherbal formulation consists immunomodulatory drugs, i.e.; Guduchi (Tinospora cordifolia Linn.), Amalaki (Emblica officinalis Linn.), and Gokshura (Tribulus terrestris Linn.).[29] This combination may be helpful to flush out the toxins from the body and correct the digestive fire, unblocks the body channels for the nutrients to reach the tissues (Strotas), and balances three fundamental bodily bio-elements (Tridosha). Its constituents individually are reported to be potent immune-modulators. This formulation is reported to possess adaptogenic and anti-ulcer activity in experimental models.[30] This formulation helps in the proper functioning of subtype of Pitta, i.e.,; Bhrajaka Pitta and giving rise to normal color, texture, and luster to skin and reduces emotional and psychological consequences.

In LC-MS analysis of the formulation Aragvadhadi Taila of present study showed vitamin D3 derivatives, i.e., 26, 26, 26, 27, 27, 27-hexafluoro-1alphaa-hydroxyvitamin D3, and alpha-(4-dimethylaminophenyl 1 alpha, 25 dihydroxy Vitamin D3.[31] Therapeutic effects of topical Vitamin D occur via Vitamin D receptor-mediated genomic mechanism resulting in inhibition of keratinocyte proliferation. Vitamin D levels have been found to be reduced in various autoimmune disorders. Hence, cow's urine and Daruharidra (Berberis aristata DC) posseses melanogenesis process due to having Vitamin D3 derivatives.[32] Derivatives of salicylic acid were found in mustard oil, Aragvadha and Dhava. It is monocarboxylic acid which causes shedding of the outer layer of skin. It may cause skin irritation (itching, inflammation) within a day or longer afterward. It is lipophilic in nature, oil soluble. Hence, it can penetrate into the pores of the skin. One it has penetrated in skin, the acid part of the molecule can dissolve some of the intracellular “glue” that holds skin cells together.[33] Mustard oil is one of the most important liquid media in this formulation. Mustard oil has a scraping action and is useful in the management of diseases caused by Kapha, dearrangement of Vata, itching, vitiligo and chronic diseases.[34] Alpha-lipoic acid (from eicosapentaenoic acid) is organo-sulfur compound with important antioxidant properties. It is present in mustard oil. Due to its properties, it can prevent the destruction of melanocytes by free radicals.[35] Cow's urine acts as chemical drug penetration enhancer and thus enhances the activity and bioavailability of the drug in the body.[36]

Adverse drug reaction

Small size blisters, irritation, itching, and rashes were found in three patients in group A [Figure 5] and 2 in group B [Figure 6]. Arsenic trisulphide is reported to cause irritation, burns, itching, and rashes on topical application.[37] Maximum patients were having excessive sun exposure (2 h to 7 h/day), and one patient had job in brass company involving work with molten brass. After blister formation, the treatment of local application was stopped till completely disappear of symptoms. For the management of the condition, affected lesions were irrigated with freshly prepared Panchavalkala decoction. Then, Yashtimadhu Churna with Ghee was applied over the affected area once a day.

Both the trial drugs; Aragvadhadi Taila (group A) and Aragvadhadi gel (group B), along with internal administration of Rasayana Churna were found highly significantly effective on improvement in VASI score, number, area and size of patches where Aragvadhadi gel was comparatively better in all above parameters and it was even comparatively better in the management of other associated signs and symptoms like Rukshata, Saparidaha and Kandu whereas Aragvadhadi Taila was better in the management of Bahalatva. Improvement in VASI (vitiligo area scoring index) score was significantly persisted till the end of follow up in patients with less chronicity and persisted even in patients with chronicity of 1–5 years and 6 -10 years. However, the findings can be revalidated through well-designed clinical trials involving a larger sample size.

Financial support and sponsorship

ITRA, Gujarat Ayurved University, Jamnagar.

Conflicts of interest

There are no conflicts of interest.

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