1. INTRODUCTION:

Siddha system of medicine is a potent and unique indigenous system of medicine, which deals with the diseases of human efficiently with the knowledge of both subtle and also the gross material body. Siddha System of medicine classified disease into 4448 types.¹ Azhal Keel Vayu (AKV) is one among 10 types of Keel Vayu particularly occurring in joints.²The clinical features of AKV are pain and swelling in the knee joints, warmth, difficulty in walking.

It can be correlated with Osteoarthritis in modern science. OA is a degenerative joint disease involving the cartilage and many of its surrounding tissues. Joint pain, stiffness and restriction of movements are the primary symptoms of knee OA.^3,4 In addition to damage and loss of articular cartilage, there is remodeling of subarticular bone, osteophyte formation, ligamentous laxity, weakening of peri-articular muscles and in some cases, synovial inflammation.^5,6In India, Overall prevalence of knee OA is found to be 28.7%.⁷ The prevalence is increased in the age group of 45-55 years.⁸The predominance is higher in female i.e. 31.6% and it is also increased in post-menopausal women.⁹

2. MATERIALS AND METHODS:

This clinical study was conducted in accordance with standard protocol after obtaining the proper approval from Institutional Ethics Committee (IEC) (F.No.NIS/Res/6-20/IEC/2012/3/01 – 23/03/2013). Raw drugs for the preparation of Pachai Karpoora Vadagam (PKV) and Vaeppa Ennai (VE) were purchased from country drug shop and authenticated. Trial medicines were prepared in Gunapadam laboratory of National Institute of Siddha, as per Siddha literature. It is an open clinical trial conducted in 40 subjects in OPD and IPD of Sirappu Maruthuvam department, Ayothidoss Pandithar Hospital, National Institute of Siddha, Tambaram sanatorium, Chennai-47. The study is registered in Clinical Trials Registry - India (ICMR-NIMS) and the Register number is CTRI/2018/06/ 014441. Universal pain assessment scale was used to assess the trial outcome.¹⁰

3. SUBJECT SELECTION:

82 subjects with the complaints of Azhal Keel Vayu (Osteoarthritis) who visited the NIS Sirappu Maruthuvam OPD, were screened as per the screening proforma. 40 trial subjects who were fulfilled the inclusion criteria and willing for written informed consent was included for the study. Among the 40, 20 subjects were treated in OPD remaining 20 were admitted in IPD. Before enrollment, the subjects were clearly informed about the objectives of study, trial drug and possible outcomes in their language. Duly signed consent form was obtained from the subjects.

3.1 Inclusion Criteria:

· Subjects aged between 30 - 60 years

· Sex: Both male and female

· Subjects having symptoms of Pain, swelling, stiffness, crepitation, restricted movements of knee joints.

· Subjects who are willing for laboratory investigation and radiological investigation.

· Subjects willing to sign the informed consent stating that He/she will conscientiously stick to the treatment during 48days, but can quit out of the trial in his/her own conscious discretion.

3.2 Exclusion Criteria: Subjects with

· Cardiac diseases

· Diabetes Mellitus

· Hypertension

· Rheumatoid arthritis, Gout, Septic arthritis.

· Psychological factor

· Use of Narcotics

· Pregnancy and lactation

· History of trauma

· Patient with any other serious systemic illness

3.3 Withdrawal Criteria:

· Intolerance to the drug and development of adverse reactions during drug trial.

· Patient with Poor compliance and defaulters.

· Patient who are unwilling to continue in the course of clinical trial.

· Occurrence of any serious illness.

4. CONDUCT OF CLINICAL STUDY:

Trial Drugs: Pachai Karpoora Vadagam (PKV) and Vaeppa Ennai (VE)

Pachaikarpoora Vadagam (PKV) (Internal Medicine)
Dosage	:	1 pills (500mg) (B.D)
Adjuvant	:	Hot water
VAEPPA ENNAI (VE) (External Medicine)
Dosage	:	50 ml
Dispensing	:	The pills were given in packets and oil was given in glass bottles.
Duration	:	48 days

After enrollment, study subjects were given with unique registration card which possess Registration number of the study, demographic details of the patient with investigator phone number. Complete clinical history, examination findings and laboratory investigations were recorded in the prescribed proforma. The duration of trial medicines was one mandalam (48 days). 14 PKV was given to subjects in B.D dosage and 50 ml VE was advised to apply on affected knee joints for 7 days. Clinical assessment was done on 1^st day and 49th day and prognosis was noted in the prescribed proforma. Laboratory investigations and Radiological investigation were done on the 0^th day and 49^th day of the trial period. Before the trial drug administration, subjects were treated with Agathiyar kuzhambu -130mg with ginger juice to balance the deranged mukkutram through purgation. Subjects were advised to take the trial drug and follow the appropriate dietary advice. After completing the full course of treatment, the subjects were asked to report on weekly interval for follow up to two months. During follow up, the subjects were enquired for the recurrence of symptoms.

5. RESULTS:

5.1 Statistical Analysis:

All collected data were entered in MS Excel and statistically analyzed by SPSS. The results were expressed in Mean±Standard Deviation. Paired ‘t’ test was performed for determining the significance between before and after treatment. A probability value of <0.05 was considered as statistical significance.

Table 1. Paired Samples‘t’ test (Pain before treatment and after treatment)

S. No	Variable	Obs	Mean±SD	t Value	p Value
1.	Before treatment	40	7.35± 0.94	20.583	p <0.001)
2.	After treatment	40	2.27 ± 1.8	20.583	p <0.001)

The mean± standard deviation of pain score at before and after the treatment were 7.35±0.94 and 2.271.8 respectively which is statistically significant (t= 20.583 p <0.001).

Table 2. Paired Samples ‘t’ test (Liver Function Test before treatment and after treatment)

S. No	Variable (Liver parameters)	Obs	Mean±SD (B.T)	Mean±SD (A.T)
1.	Total Bilirubin	40	0.69±0.17	0.67±0.19
2.	SGOT	40	19.92±4.32	18.42±4.37
3.	SGPT	40	19.1± 6.19	18.53±6.21
4.	Alkaline Phosphates	40	95.6± 9.71	88.33±11.51
5.	Total Protein	40	6.68±0.56	6.21±1.53

Where p<0.001, p<0.05 denotes the values are statistically significant

Table 3. Paired Samples ‘t’ test (Renal Function Test before treatment and after treatment)

S.No

Variable

(Renal parameters)

Obs

Mean±SD

(B.T)

Mean±SD

(A.T)

Serum Urea

19.62±4.127

19.32±3.36

Serum Creatinine

0.8±0.09

0.71±.16

Where p<0.001, p<0.05 denotes the values are statistically significant

Fig 1. Pain assessment by Universal pain assessment scale

Fig 2. Assessment of clinical features before and after treatment

Fig 3. Compiled outcome of completed trial

6. DISCUSSION:

The present study was aimed to evaluate a safe and effective treatment for managing Azhal Keel Vayu (Osteoarthritis). The trial drugs were effective in reducing the intensity of pain and improve the movements of knee joints in the treatment of AKV. In this clinical trial the prevalence was higher in female group and 30% of trial subjects had attained menopause with Obesity. Oestrogen depletion may directly increase cartilage damage and subchondral bone loss or increase susceptibility for an additional trigger.¹¹ Preliminary Phytochemical analysis of the PKV reveals the presence of Alkaloids, Phosphate, Ammonium and Tannic acid. The ingredients of PKV possess the anti-oxidant, analgesic, anti-inflammatory, anxiolytic, antidepressant, hepatoprotective, antiseptic, stomachic, anti-viral and anti-herpetic activities.^12,,13 KUMAR et al. and Naik et al. Reveled the anti-inflammatory and analgesics activities of Neem oil in animal models.^14,15 So, the external medicines itself possessed the anti-inflammatory and analgesics activities. Table 1 revealed that the pain score on before and after treatment was statistically significant. It was observed from the present clinical study, the synergistic effect of the herbs and minerals present in the trial drugs has supported to the overall anti‑inflammatory and analgesic activities of the formulations. Table 2 and table 3 revealed the insignificant of RFT and LFT. The Acute toxicity study of the internal medicine reveals that the drug was safe in animal models.¹⁶ No adverse effect and complaints of deterioration were observed during the study including follow up period. Trial subjects responded well to the trial drugs and felt comfortable during the trial period.

7. CONCLUSION:

The results of the clinical study showed significant reduction of intensity of pain, good improvement in the restriction of movement and clinical symptom. There is a statistically significant results were noted in the pain score before and after treatment. The safety parameters of trial subjects were found to be insignificant. Hence, it may be concluded that the Siddha Herbo-mineral formulations are affordable, effective and safe for Azhal Keel Vayu (osteoarthritis) management.

8. REFERENCE:

1. Kandaswamy Pillai N, History of Siddha Medicine, Published by Government of Tamilnadu, 1979.

2. Siddha Maruthuvam Pothu, Ka. Na Kuppusamymuthaliyar.; 7th edition; Page no: 626-627; Pub: Deparment of Indian medicine and Homeopathy, Chennai – 600106.

3. Rachel Wittenauer et al., Priority Medicines for Europe and the World . A Public Health Approach to Innovation", Background Paper 6.12, Osteoarthritis, January 28th 2013.

4. Behzad Heidari. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I, Caspian J Intern Med. 2011; 2(2): 205-212.

5. Anna Litwic, et al., Epidemiology and Burden of Osteoarthritis, The MRC Lifecourse Epidemiology Unit, (University of Southampton), Southampton General Hospital, Southampton SO16 6YD, UK. 7. 2013 July 20.

6. Kanchan R Pagar, Sarika V Khandbahale, Poonam M Kasar. Osteoarthritis: Pathophysiology and Current Treatment Modalities. Asian J. Pharm. Res. 2019; 9(4):289-298.

7. Dr.Chandraprakash pal et al., Epidemiology of knee osteoarthritis in India and related factors, Indian J Orthop. 2016; 50(5): 518–522.

8. Sarumathy S., CH Haripriya, Muddala Vara Prasanna Rao, Gayathri K., CH Bala Sudhakar, Divya M., Shanmugasundaram P. Clinical Comparison of the Efficacy and Safety of Intra-Articular Injections of Sodium Hyaluronate and Methyl Prednisolone in the Treatment of Osteoarthritis of Knee. Research J. Pharm. and Tech. 2015; 8(11): 1526-1528

9. Gopinathan NR, Sen RK, Behera P, Aggarwal S, Khandelwal N, Sen M. Awareness of osteoporosis in postmenopausal Indian women: An evaluation of Osteoporosis Health Belief Scale. J Mid-life Health 2016; 7:180-4.

10. Instruments, Pain Intensity. "0–10 Numeric Rating Scale (page." (2003).

11. Sniekers, Y.H., Weinans, H., van Osch, G.J. et al. Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis. Arthritis Res Ther. 12, R182 (2010). https://doi.org/10.1186/ar3148

12. Soane K.M. Chaves, Chistiane M. Feitosa and Lidiane da S. Araújo, Alkaloids Pharmacological Activities - Prospects for the Development of Phyto pharmaceuticals for Neurodegenerative Diseases. Current Pharmaceutical Biotechnology. 2016; 17 (7): 629-635.

13. Kumar, Rakesh, Anjum, Nishat and Tripathi, Yogesh. Phytochemistry and Pharmacology of Santalum album L.: A Review. World Journal of Pharmaceutical Research. 2015; 4: 1842-1876.

14. Kumar, Sanjay, et al. Analgesic effect of neem (Azadirachta indica) seed oil on albino rats. Pain 7 (1946).

15. Naik, Manas Ranjan, et al. Study of anti-inflammatory effect of neem seed oil (Azadirachta indica) on infected albino rats. Journal of Health Research and Reviews. 2014; 1.3: 66.

16. Shunmugaram, S. Physiochemical and Acute Toxicity Analysis of a Siddha Herbo-Mineral Formulation-Pachai Karpoora Vadagam (PKV). Research Journal of Pharmacy and Technology. 2019; 12.1: 227-230.

Received on 08.10.2020 Modified on 27.04.2021

Research J. Pharm.and Tech 2022; 15(2):611-614.

DOI: 10.52711/0974-360X.2022.00100