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Anti-Inflammatory Properties of a Processed Copper Complex in L-Arginine Induced Pancreatitis -Two Experimental Studies

Authors:
  • VCP Cancer Research Foundation
  • VCP Cancer Research Foundation, Dehradun
  • Padaav Speciality Ayurvedic Treatment Center
  • Vcp cancer research center

Abstract and Figures

Background: Recurrent Acute/Chronic Pancreatitis (RA/CP) is an inflammatory disorder of the pancreas. The disease is progressive in nature and may turn fatal in due course. The aetiology of this inflammatory condition majorly remains mysterious, especially in Indian context, where majority of the patients of RA/CP are non-alcoholics and non-tobacco users with no family history of the disease. An Ayurvedic Mineral Complex (AMC) has shown significant improvement in the clinical conditions of pancreatitis patients and significantly reduced acute exacerbations and emergency hospitalizations in a number of cases. The present set of studies was carried to understand the mechanism of AMC. Methodology: AMC was evaluated for its pancreatitis protective properties at different doses in an existing model of L-Arginine induced pancreatitis in albino male wistar rats and compared to Methylprednisolone, a known anti-inflammatory agent. The study was carried in two phases, with three different doses of AMC used in each phase. Results: The studies indicate that AMC was well tolerated. It did not cause mortality or any clinical signs of toxicity in male wistar rats, who were given a daily dose of AMC for twenty-one days. There was no change in body weight and food consumption pattern. It also decreased the oxidative stress, inflammatory cytokines and severity of inflammatory condition in pancreas by reducing structural changes. The best pancreatitis protective effect of AMC was observed at doses of 25 mg/kg and 19 mg/kg body weight. Conclusion: The results of the aforesaid studies validate the stated clinical efficacy of AMC by showing its strong pancreatitis protective properties. AMC might be developed as a potential anti-inflammatory agent.
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OPEN ACCESS EC GASTROENTEROLOGY AND DIGESTIVE SYSTEM
Research Article


1234
1Director, VCPC Research Foundation, Uttarakhand, India
2Assistant Manager, Clinical Research, VCPC Research Foundation, Uttarakhand, India
3Ayurvedic Consultant, Padaav - Speciality Ayurvedic Treatment Centre, Uttarakhand, India
4Manager, Clinical Services, Padaav - Speciality Ayurvedic Treatment Centre, Uttarakhand, India
*: Vaidya Balendu Prakash, Director, VCPC Research Foundation, Uttarakhand, India.
May 20, 2019
Abstract
-

   



            




-

-

Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).
Keywords: Pancreatitis; Ayurveda; Rasa Shastra; Chronic; Mineral Complex



as 
      
               


Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).



 


    

access to these.

ho
Luffa echinata and Clitorea ternatea



vide 
res

we
  


   
G1 - Untreated control - 21 6
G2 - Disease control  6
  6
  6
  6
  6
Table 1a: Details of groups and dose schedule in Phase I.
*In G6, the treatment had to be terminated after 14 days, which was considered humane
endpoint due to >20% weight loss in the animals [21].
s  
G1 - Untreated control - 21 6
G2 - Disease control  6
  6
  6
  6
  6
Table 1b: Details of groups and dose schedule in Phase II.
*Considering the outcomes in Phase I, Methylprednisolone was dosed at 15 mg/kg in G6 Phase II. However, the treatment could be carried
for 18 days only, which was considered as humane end point due to > 20% weight loss in animals [21].
Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).


           




-

-
ist
   








  
dis
               


Figure 1a: Graphical representation of results of histopathology reports in the groups - Phase I.


Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).
Figure 2a and 2b: 


almost normal tissue architecture.
Figure 1b: Graphical representation of results of histopathology reports in the groups - Phase II.


Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).

       

        
   

    -

   

-

 Rasa Shastra in Ayurveda  
wRasa Shastra

   
toshoth nashak

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         
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Rasa Shastra
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
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


1. Busnardo AC., et alAmerican Journal of Surgery 
2. et alJournal of the American Medical Association
3. 
4.   et al           Gut


Citation: Vaidya Balendu Prakash., et al.
EC Gastroenterology and Digestive System 6.7 (2019).

., et al.
5. et alInternational
Journal of Clinical and Experimental Pathology 
6. et al
7. et alAmerican Journal of Therapeutics 
e1921.
8. Craik CS., et al
9. Ianiro G., et alCurrent Drug Metabolism 
10. Prakash VB., et al  
 7.2 (2017): e9.
11. Prakash VB., et al-
Pancreatic Disorders and Therapy
12.  et al    
Journal of the Pancreas 
13. Otsuki M., et alGastroenterology Research and Practice 
14. et al
Laboratory Investigation
15. et alInternational Journal for Pharmaceu-

16. African Journal of Traditional, Com-
plementary and Alternative Medicines 
17. Tchounwou PB., et alExperientia Supplementum 
18. Badiye A., et alResearch Journal of Recent Sciences 
19. et al
20. Thunus L., et al Analyst
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21. 

... In addition, the composition is completely safe and shows preventive qualities against pancreatitis [9] . A new finding employing Ayurvedic preparation in pancreatitis patients is the reducing effect of CA 19-9. ...
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A carbohydrate antigen called CA19-9 is used to identify pancreatic cancer patients. Pancreatic cancer patients and those with some other gastrointestinal carcinomas have been reported to have increased levels of CA19-9. Additionally, recent research suggests that this antigen plays an etiological function in pancreatitis and pancreatic cancer. Decreasing levels of the marker are indicative of a good prognosis and are commonly used to evaluate the effectiveness of therapies offered for pancreatic cancer. Lowering CA19-9 levels in patients with pancreatitis from the start of treatment has been demonstrated to be successful using Ayurvedic approaches. Research on this formulation as a preventive treatment for pancreatic cancer in people with pancreatitis may find fresh direction as a result of this observation. In this case report, the author and his team discuss Ayurvedic features of patient treatment through the use of Ayurvedic therapy. The pancreatitis patient with increased CA 19-9 levels who received treatment with Ayurvedic medicines is the subject of this report's observations.
... AMAR is prepared using copper, mercury, and sulfur but does not show the presence of free metals in the finished form [5]. The formulation has demonstrated pancreatitis protective properties in experimental models [9]. The case report suggests that the formulation might have contributed to the improvement in the clinical condition of the boy, as well as the reduction in the size of the main pancreatic duct. ...
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The case report presented here highlights the use of an Ayurvedic treatment protocol (ATP) in managing hereditary pancreatitis (HP) in a 14-year-old boy. HP is a rare form of pancreatitis caused by specific gene mutations that are inherited within families. It is known to be aggressive and can lead to pancreatic cancer in later stages. The boy, in this case, experienced multiple episodes of pancreatitis and required several hospitalizations despite following a conventional treatment approach, which included a dairy-free, protein and fat-restricted diet, and pancreatic enzyme supplementation. However, after starting the ATP in February 2022, which involved a modified diet and the use of herbo-mineral Ayurvedic formulations, the boy reported significant improvement in his general well-being and was able to lead a normal life without experiencing any discomfort. The ATP included a customized diet comprising dairy products with moderate amounts of fat and protein, along with specific herbo-mineral formulations and the withdrawal of pancreatic enzymes. The boy also received vitamin D3 supplementation. After approximately one year of following the ATP, the disease progression was arrested, as indicated by follow-up images and investigations. The size of the pancreatic duct decreased from 8 mm to 2.8 mm. This case report suggests that the ATP may have potential efficacy in managing hereditary pancreatitis and halting disease progression. However, it is important to note that this is a single case report, and further research and clinical studies are needed to validate the long-term benefits and understand the underlying mechanisms of Ayurvedic interventions in hereditary pancreatitis.
... It is imperative to mention that CA19-9 lowering effect seen in this case report is in continuation to the earlier studyadding to the therapeutic values of metal based Ayurvedic formulations 17 . Similarly, MBAF have also demonstrated pancreatitis protective properties in experimental studies 18 . This case report might be an add on to anecdotal evidencesrelated to the role of Ayurvedic interventions in the management of Pancreatitis. ...
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Pancreatitis is an inflammatory and irreversible disorder of Pancreas, though unpredictable in nature. It's broadly categorized in acute and chronic pancreatitis depending upon the diagnostic parameters. Both types of pancreatitis are managed by using tools of conventional treatment; however natural course of progression of the diseases process remains unbeatable. Pancreatitis may also lead to pancreatic cancer and a tumor marker called Carbohydrate 19-9 antigen (CA 19-9) is being used routinely to accesses the progression of the disease. The normal value of CA 19-9 in the serum is<37 U/mL, whereas, levels more than 300 U/mL are considered definite indicators of pancreatic cancer. Here, we report a case of 52 years old male form Eastern Uttar Pradesh in India who was initially diagnosed for Acute Necrotizing pancreatitis and was treated conservatively by subject experts. Later he suffered with seven more episodes within three years of initial diagnosis and was dealt in emergencies. His clinical condition continued to deteriorate and he lost 15 kg body weight during the course of disease. At this juncture, he opted to a north India based specialty Ayurvedic treatment centre and was treated with metal based Ayurvedic formulations, daily diet of 2000 to 2200 calories and complete mental and physical rest. He responded well to Ayurvedic treatment protocol (ATP) and showed overall improvement. There was also remarkable improvement in his rising CA 19-9 levels, that turned to normal in the first hundred eight days of ATP, which needs to be explored further for its path making therapeutic values.
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Background: Recurrent Acute/Chronic Pancreatitis (RA/CP) is an inflammatory disorder of the pancreas. The disease is progressive in nature and may turn fatal in due course. The aetiology of this inflammatory condition majorly remains mysterious, especially in Indian context, where majority of the patients of RA/CP are non-alcoholics and non-tobacco users with no family history of the disease. An Ayurvedic Mineral Complex (AMC) has shown significant improvement in the clinical conditions of pancreatitis patients and significantly reduced acute exacerbations and emergency hospitalizations in a number of cases. The present set of studies was carried to understand the mechanism of AMC. Methodology: AMC was evaluated for its pancreatitis protective properties at different doses in an existing model of L-Arginine induced pancreatitis in albino male wistar rats and compared to Methylprednisolone, a known anti-inflammatory agent. The study was carried in two phases, with three different doses of AMC used in each phase. Results: The studies indicate that AMC was well tolerated. It did not cause mortality or any clinical signs of toxicity in male wistar rats, who were given a daily dose of AMC for twenty-one days. There was no change in body weight and food consumption pattern. It also decreased the oxidative stress, inflammatory cytokines and severity of inflammatory condition in pancreas by reducing structural changes. The best pancreatitis protective effect of AMC was observed at doses of 25 mg/kg and 19 mg/kg body weight. Conclusion: The results of the aforesaid studies validate the stated clinical efficacy of AMC by showing its strong pancreatitis protective properties. AMC might be developed as a potential anti-inflammatory agent.
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Pancreatitis is an inflammatory disorder of the pancreas, affecting its endocrine and exocrine function. It is mainly associated with abdominal pain, vomiting, nausea, indigestion, steatorrhea, weight loss and diabetes. There are many variants of pancreatitis that have been broadly divided into acute and chronic pancreatitis. In both the conditions, patients may suffer with recurring episodes of the aforesaid symptoms with progression of the disease. Pancreatitis is conservatively managed by emergency hospitalizations, lifelong pancreatic enzymes and supplements with modifications in diet and lifestyle. Advance surgical intervention is also being used in some cases to provide long term solution. However, the benefits of such procedures are limited to certain pockets of the world. Owing to unpredictable nature of the disease and limitations of treatment possibilities, pancreatitis adversely affects psychological, physical and financial status of the patients. In this scenario, many patients opt for alternate medicines. A North India based Ayurvedic clinic has earned reputation in bringing complete and sustainable relief in significant number of cases of Recurrent Acute/ Chronic Pancreatitis (RA/CP). A data on 319 well diagnosed cases demonstrates that Ayurvedic Treatment Protocol (ATP) has been able to bring complete relief in significant number of patients, without causing any side effect. Statistical analysis of the data shows that the treatment brought significant improvement in weight and reduction in frequency of attacks. ATP comprises of a few Ayurvedic formulations that are prescribed for a period of one year, along with regulated diet and lifestyle as well as complete physical and mental rest. The main Ayurvedic formulation used in the treatment is Amar. Experimental studies conducted using Amar have demonstrated its protective properties against pancreatitis. Further research is being conducted for the systematic and scientific development of this specialized ATP.
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Aim To establish non-invasive chronic pancreatitis model of Rat. Methods Thirty wistar rats (200±50 gm) were given L-arginine hydrochloride (250 mg/100 gm b.wt./day) intraperitoneally in two repeated doses of 1 hour interval on day 1 and repeated with same single dose on day 4,7,10,13,16 and 19. Six animals were sacrificed on day 3, 6 animals on day 9, 6 animals on day 15 whereas rest 6 animals were sacrificed on day 21. Six control rats received sham injections of normal saline and sacrificed on day 21. Biochemical, histopathological, Immunohistochemistry staining for activated pancreatic stellate cells and mRNA expression for TGF-β1, Collagen 1α 1 and Fibronectin 1 were done. Results Pancreas in control group was soft grey with mean weight 3.0±0.19 gm. While, on day 15 and 21, pancreas were small, firm to fatty and weighed 1.9±0.23 gm and 1.8±0.19 gm respectively. Interlobular and intralobular fibrosis replaced 30% of exocrine pancreas after 5 injections on day 15. Inflammation comprised of biliophages and eosinophils along with lymphoplasmacytic cells. Fat infiltration (5-10%) was seen only in 1 case on day 15. However all animals showed marked fibrosis. With continuation of repeated acute injury till day 19, exocrine pancreas showed extensive fat infiltration (30-50%) in addition to fibro inflammatory changes. Only 5-10% of normal exocrine parenchyma persisted till day 21. TNF-α, IL-10 and lipid peroxidation levels were significantly elevated and GSH levels were significantly low in arginine treated animals. IHC staining showed α-SMA (+) activated pancreatic stellate cells on day 15 and day 21. Expression of TGF-β1, Collagen 1α 1 and Fibronectin 1 were also found to be significantly elevated on day 15 and day 21. Conclusion Normal pancreatic exocrine tissue was replaced by fibrosis and inflammation at day 15 after repeated acute injury which when continued till day 21 showed significant fat infiltration and fibrosis.
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Recurrent Acute Pancreatitis/ Chronic Pancreatitis (RAP/ CP) is generally marked by sudden onset of symptoms like severe abdominal pain, vomiting and weight loss that needs emergency hospitalization. Owing to irreversible and progressive nature of the disease and limitations of conventional treatment, many patients look for an alternative solution. Here, we report data of 250 well diagnosed cases of acute recurring/ chronic pancreatitis, enrolled in between January 1997 to August 2016, in our Ayurvedic clinical practice in Northern part of India. Ayurveda is well recognized as an independent medical system parallel to conventional medicines in India and a subject is free to opt for any system of medicine for the prevention and treatment of any ailment. The subjects were treated with a complex herbo-mineral formulation based on the principles of Rasa Shastra in Ayurveda that deals with the therapeutics of processed metals in the prevention and treatment of diseases. They were also prescribed a regulated balanced diet and lifestyle. Significant improvement has been noted in subjects who have completed the treatment.
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Background: Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. Methods: This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (β-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. Results: Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. Conclusion: New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future.
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