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Abstract

Peptic ulcers, characterized by mucosal erosion in the stomach or duodenum, continue to pose significant health challenges worldwide. .Allylpyrocatechol, the active component obtained from ethanol extract of leaves of Piper betle. The study investigates the healing properties of a specific compound, allylpyrocatechol, which is derived from Piper betel. This compound is evaluated for its effectiveness against stomach ulceration induced by aspirin , a nonsteroidal anti-inflammatory drug (NSAID) known to cause gastric ulcers . allyl pyrocatechol (APC), the major antioxidant constituent of Piper betel, growth factors (EGF, EGF-R, SMAD-4) and cyclooxygenases (COX-1 and COX-2) were observed to be up-regulated in presence of APC during healing process.

Keywords

erosion ,allylpyrocatechol ,piper betel, stomach ulceration ,anti-inflammatory, antioxidant, cyclooxygenase.

Introduction

Gastric ulcers are painful sores that develop on the lining of the stomach. They can be caused by various factors, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin, which can lead to stomach damage and delayed healing. This is a significant health issue, including gastric ulcers [1]. as many people rely on NSAIDs for pain relief but may suffer from their side effects.(1) which are very commonly taken by the people as pain-killers. The NSAIDs induce ulcer by several mechanisms, one being the involvement of free radicals by neutrophil activation. The free radical damage occurs mainly by the lipid peroxidation. There has been an accumulative evidence of the involvement of prostaglandin, cyclooxygenase 1 & 2, Nitric oxide, inducible Nitric oxide synthatase and different cytokines are induced or increased by gastric ulceration and might also contribute ulcer healing. There is a cross-over role of COX-1 and COX-2 (2) Piper betel leave extract contains large number of bioactive molecule like polyphenol, alkaloids, steroids, saponin and tannin. Piper betel has light yellow aromatic essential oil with sharp burning taste. The main constituents are Hydroxychavicol (HC)/Hydroxychavicol acetate (HCA), Allylpyrocatechol (APC) (3) Consequently, prevention of gastrointestinal disorder continues to be of concern for both medical professionals and researchers. Various synthetic anti-ulcer drugs are presently available, and some of these like misoprostol are specifically used to prevent or treat the NSAID induced gastric ulcer. However, each of these drugs confers simpler to severe side effects such as diarrhea, itching, skin rash, dizziness, and inactivation of some antifungal drugs (proton pump inhibitors), confusion in elderly patients, headache and antiandrogenic effect (H-2 receptor blockers), constipation, vomiting, indigestion, back pain, and dizziness (sucralfate), bleeding diathesis and abortion for pregnant women (misoprostol)[4] Thus, there is a growing interest on non-toxic, antiulcer formulations from medicinal plants, and many taxa of medicinal plants have been assessed worldwide for their antiulcerogenic effectsIn the developing nations, this turn of events has also been prompted, in part, by the high cost of the modern antiulcer medication.

Peptic Ulcer :-

is a common gastrointestinal tract (GIT) disorder that affect about 10% of the world population . It’s characterized by GIT bleeding   perforation and erosion of the mucosa wall due to imbalance between aggressive (acid, pepsin and Helicobacter pylori) and defensive factors (mucin, prostaglandin  ,bicarbonate ,nitric oxide , mucosal blood flow and growth factors) . [8] Peptic ulcer is an acid-induced lesion of the digestive tract that is usually located in the stomach or proximal duodenum, and is characterized by denuded mucosa with the defect extending into the submucosa or muscularis propria [9] Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic.[10]

common signs and symptoms include:-

  • Epigastric abdominal pain
  • Bloating
  • Abdominal fullness
  • Nausea and vomiting
  • Weight loss/weight gain

Aspirin Induced Peptic Ulcer :-

       
            fig-1.png
       
           
            fig-2.png
       
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of pain and inflammation. Their use may result in gastroduodenal side effects(5) The current work was aimed to study the protective role of PRP on gastric ulcer induced by aspirin.

Materials and Methods: Forty adult male albino rats were divided into four groups. Group I; sham control, group II received PRP, group III received aspirin for induction of gastric ulcer and group IV was provided with PRP then received aspirin. All rats were sacrificed then the fundic mucosa was processed for light and scanning electron microscopic study.(6)

Mechanism :- Reduced Mucosal Defense – Prostaglandins maintain mucus and bicarbonate secretion, which protect the stomach lining. With lower levels, the mucosal barrier weakens.

Piper Betel :-

Piper betle L. (synonym: Piper betel Blanco) (Piperaceae) is a widely known perennial creeping plant belonging to the genus Piperaceae and originates from central and eastern Peninsular Malaysia and is distributed to East Africa and tropical countries of Asia.

       
            fig-3.png
       
Taxonomy

Kingdom: Plantae

Division: Magnoliophyta

 Class: Magnoliopsida

Order: Piperales

Family: Piperaceae

Genus: Piper Species: Piper betle L.(8)

Distribution And Cultivation

The betel vine is believed to have originated in Malaysia.(9) The plant is widely grown in forests that are generally damp and also in hot and moist climatic conditions of India and many other countries in South and South East Asia, viz. China and Vietnam. Piper betle is believed to have first emerged in tropical Asia and then spread to East Africa and Madagascar. Betel is widely grown in India, Sri Lanka, Bangladesh, Indonesia, Nepal, Pakistan, Vietnam, Thailand, Laos, Kampuchea, Philippine Islands, Burma, Malaysia, Taiwan, Malay Peninsula and many countries in Southeast Asia and is known to have a long history, mentioning the presence of the betel plant over 2000 years.(10)

Microscopic Charactristics: -

Sr. No.

Parameters

Observation of Leaf

1

Color

Yellowish Green -Dark Green

2

Oduor

Characteristic and pleasant

3

Taste

Sweet to Pungent

4

Shape

Heart shape

5

Texture

Glossy, smooth

6

Venation

Reticulate 8 Apex Pointed

Traditional Uses:-

The oral cavity, which forms the initial part of the gastrointestinal tract, is an important organ involved in dietary intake, digestion. The oral cavity is affected by various ailments and globally dental caries, oral wounds, halitosis and cancer are some of the most common. Since time immemorial, humans have been using plants as dietary agents and the Indian indigenous plant Piper betel , commonly known as betel leaf, has been widely used in orodental care in the traditional Indian system of medicine Ayurveda.

Collection: -

  1. Early Morning: Betel leaves should ideally be collected early in the morning when they are fresh and have high moisture content. During this time, the leaves are more potent and richer in essential oils.
  2. Young Leaves: The most medicinally potent leaves are usually young, tender ones that are not too mature. Older leaves might lose some of their medicinal properties.
  3. Post-Rain Season: In many tropical areas, the period right after the monsoon season (when the plants are healthy and lush) is considered a good time for harvesting, as the leaves tend to be fuller and contain more active compounds.

Seasonal Considerations:

  • Rainy Season (Monsoon): In many tropical regions, the rainy season is the peak growing period for betel leaves. The plants receive abundant water and nutrients, leading to better leaf quality. This season is typically preferred for collecting leaves, as they are more vibrant and packed with bioactive compounds.
  • Dry Season: During dry seasons, the leaves might become tougher and drier, reducing their medicinal potency. However, they can still be used, especially if no other fresh leaves are available.

Harvesting Guidelines for Medicinal Use:

  • Fresh Leaves: For most medicinal applications, fresh betel leaves are preferred, as they contain more moisture and active ingredients.

Chemical Constituents: -

Compound

Chemical structure

Biological properties

Application

Eugenol

 

 

 

 

Anti-inflammatory, antimicrobial, antiviral, anti-mutagenic, analgesic, antioxidant, anti-carcinogenic, antiseptic, antidepressant, insecticidal, fungicide

Pain killer
oral hygiene

Hydroxy chavicol

 

 

 

Anti-inflammatory, antioxidant, antimutagenic, antibacterial, Anti-carcinogenic, antithrombotic, and gastric ulcer-healing activity.

Antimutagenic activity, use in mouthwash

for preventing and treating oral infections.

 

Methyl eugenol

 

 

 

anti-inflammatory, cytotoxic against human cell lines, insecticidal activity

Used as Fragrances and

perfumery, toiletries,

and detergents

Chavibetol

 

 

 

Noncentral analgesic, antipyretic, anti-inflammatory, antibacterial, antineoplastic

Used as EO
The volatile and aromatic component

?- caryophyllene

 

 

 

Anti-inflammatory, anti-carcinogenic, pain relief, primary therapeutic against atherosclerosis and osteoporosis

Used to prevent diabetes, endometriosis

cerebral ischemia, anxiety and depression,

liver fibrosis, and Alzheimer-like disease.

Chavicol

 

 

 

Antimicrobial, antioxidant, antiseptic

used as an odorant in perfumery and as a

Flavor

Safrole

 

 

 

Anti-inflammatory, detoxifying agent, antioxidant, antimicrobial, antimutagenic, immunosuppressive

beverage and candy preparation but carcino

genic to rats (not to humans).

Estragole

 

 

 

Antimutagenic, antifungal against some bacteria

Used as a flavoring agent, food additive,

and EO

Allylpyrocatechol: -

       
            fig-4.png
       
       
            fig-5.png
       
The general structure of a 4-alkylcatechol can be represented as 4-alkyl-1,2-benzenediol. The "alkyl" group can vary, leading to different specific names. For example:(11)

  • 4-Methylcatechol: 4-Methyl-1,2-benzenediol
  • 4-Ethylcatechol: 4-Ethyl-1,2-benzenediol
  • 4-Propylcatechol: 4-Propyl-1,2-benzenediol

allypyrocatechol, also known as 4-allyl-1,2-benzenediol, is a compound that belongs to the catechol family, which is characterized by the presence of a catechol moiety

       
            fig-6.png
       
APC's Effects:

    • Anti-inflammatory:

 selectively Inhibits COX-2, reducing prostaglandin E2 PGI2(prostacyclin).

    • Gastroprotective:

Enhances mucin production, creating a protective gastric layer.

    • Antioxidant:

Neutralizes free radicals, reducing oxidative stress.

    • Hepatoprotective:

Prevents liver damage from reactive oxygen species (ROS).

Property

Ranges

Molecular Formula: -

C9H10O2

Molecular Weight: -

150.17 g/mol

Appearance

White gray to crystalline powder

purity (GC)

mini. 98.0 %

Melting point

43.0 to 49.0 °C

Boiling Point

123 °C/2 mmHg

Condition to Avoid

Heat Sensitive

 

Interaction

Effect

Example

NSAIDs (e.g., Aspirin)

Synergistic anti-inflammatory

Aspirin + Allylpyrocatechol: Enhanced anti-inflammatory effects

Antioxidants (e.g., Vitamin C, Vitamin E)

Synergistic antioxidant effect

Vitamin C + APC: Combined antioxidant effect in inflammatory conditions

Proton Pump Inhibitors (PPIs)

Synergistic gastroprotective

Omeprazole + APC: Enhanced protection against gastric ulcers

Antiplatelet Drugs (e.g., Clopidogrel)

Mildly enhanced antiplatelet effect

Aspirin + APC: Potential increased bleeding risk

Extraction of APC from Piper Betel

  • Source of APC: Allylpyrocatechol (APC) is derived from the leaves of the Piper betel plant, which is commonly used in South East Asia as a mouth freshener. The leaves are known for their various health benefits, including antioxidant properties [12].
  • Extraction Method: The technique used to extract APC is ethanol extraction. This involves using ethanol as a solvent to dissolve the active compounds present in the dried leaves. Ethanol is effective because it can extract a wide range of phytochemicals, including phenolic compounds like APC 
  • Process of Extraction:
    • Drying the Leaves: The first step is to air-dry the Piper betel leaves. This helps to preserve the active compounds and makes them easier to extract. Air-drying is a gentle method that minimizes the loss of sensitive phytochemicals 
    • Ethanol Extraction: Once the leaves are dried, they are soaked in ethanol. The ethanol penetrates the plant material and dissolves the desired compounds, including APC. This process allows for the concentration of beneficial substances from the leaves 

Final Product: The resulting ethanol extract contains APC along with other phytochemicals. This extract can then be used for further research or therapeutic applications, particularly in studying its antioxidant and healing properties

CONCLUSION: -

In this project we concluded that anti inflammatory action and gastroprotective action of APC  from herbal origin are prepared and hence we can conclude that the piper betel leaves shows the anti inflammatory and gastroprotective properties that can use in inflammation and peptic ulcer APC syrup shows better activity less side effect compare to  marketed aspirin. Frequently Aspirin intake causes the peptic ulcer due to APC syrup is safe in inflammation also in peptic ulcer.

Oral administration of APC at different doses accelerated the rate of healing of gastric lesion induced by aspirin  reduction in the production of NO, PGE2 and reduce expression of NF-?B. To conclude, the hydroalcoholic extract of Piper betel showed significant antiulcer activity in various experimental models of ulcer in rats suggesting its main mechanism of anti-ulcerogenic effect probably due to APC present in the extract.

Herbal syrup of piper betel (APC) is safe for consumers and children and older patients in inflammatory condition or peptic ulcer show better threpeutic activity than the marketed formulation also hepatoprotective action no any side effect safe for use .

REFERENCES

  1. Debashish Banerjee,Sayanti bhattacharya ,Sandip k.Biochemical Mechanism of Healing Activity of the Natural Phenolic, Allylpyrocatechol Against Indomethacin-Induced Gastric Ulceration in Mice 22 April 2008- Vol. 53, Iss: 11, pp 2868-2877
  2. Pace V. Use of Nonsteroidal anti inflammatory drugs in cancer.Palliat Med 1995; 9:273-286.
  3. Chandra, V., Tripathi, S., Verma, N. K., Singh, D. P., Chaudhary, S. K., & Roshan, A. (2012). Piper betel: Phytochemistry, traditional use & pharmacological activity – A review. International Journal of Pharmaceutical Research and Development (IJPRD), 4(04), 216-223.
  4. Miederer SE. Will anti-ulcer drugs soon differ only in their side effects? Fortschr Med. 1986;104:918–920. [PubMed] [Google Scholar]
  5. Leung, Anna M., Maria J. Redlak, and Thomas A. Miller. "Aspirin-Induced Mucosal Cell Death in Human Gastric Cells: Role of a Caspase-Independent Mechanism." Digestive Diseases and Sciences, vol. 54, no. 1, 2008, pp. 28–35.
  6. Leung, Anna M., Maria J. Redlak, and Thomas A. Miller. "Aspirin-Induced Mucosal Cell Death in Human Gastric Cells: Role of a Caspase-Independent Mechanism." Digestive Diseases and Sciences 54, no. 1 (2008): 28–35.
  7. Madhumita M, Guha P, Nag A. Extraction of betel leaves (Piper betle L.) essential oil and its bio-actives identification: Process optimization, GC-MS analysis and anti-microbial activity. Ind. Crops Prod. 2019;138:111578.
  8. Cronquist A. An Integrated System of Classification of Flowering Plants. Columbia University Press; 1981.
  9. Chattapdayay SP, Maity S. Diseases of Betelvine and Species. ICAR; 1967.
  10. Biswas, P., Anand, U., Chatterjee Saha, S., Kant, N., Mishra, T., Masih, H., Bar, A., Pandey, D. K., Jha, N. K., Majumder, M., & Das, N. (2022). Betelvine (Piper betle L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes. Journal of Cellular and Molecular Medicine, 26(8),
  11. Furukawa Y, Fukazawa N, Miyama Y, Hayashi K, Furukawa S. Stimulatory effect of 4-alkylcatechols and their diacetylated derivatives on the synthesis of nerve growth factor. Biochem Pharmacol. 1990;40(10):2337–2342.
  12. Banerjee, Debashish, et al. "Biochemical Mechanism of Healing Activity of the Natural Phenolic, Allylpyrocatechol Against Indomethacin-Induced Gastric Ulceration in Mice." Digestive Diseases and Sciences, vol. 53, no. 11, 2008, pp. 2868–2877.
  13. Bhattacharya S, Banerjee D, Bauri AK. Healing property of the Piper betel phenol, allyl pyrocatechol against indomethacin-induced stomach ulceration and mechanism of action. World J Gastroenterol. 2007;13(27):3705–3713. doi: 10.3748/wjg.v13.i27.3705.
  14. Pace V. Use of nonsteroidal anti-inflammatory drugs in cancer. Palliat Med. 1995;9:273–286. doi: 10.1177/026921639500900402.
  15. Garner A. Adaptation in the pharmaceutical industry, with particular reference to gastrointestinal drugs and diseases. Scand J Gastroenterol Suppl. 1992;193:83–89. doi: 10.3109/00365529209096011.
  16. Dhikav V, Singh S, Pande S, Chawla A, Anand KS. Non-steroidal drug-induced gastrointestinal toxicity: Mechanisms and management. J Indian Clin Med. 2003;4:315–322.
  17. Miederer SE. Will anti-ulcer drugs soon differ only in their side effects? Fortschr Med. 1986;104:918–920.
  18. Borrelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res. 2000;14:581–591. doi: 10.1002/1099-1573(200012)14:8<581>3.0.co;2-s.
  19. Majumdar B, Ray Chaudhuri SG, Ray A, Bandyopadhyay SK. Effect of ethanol extract of Piper betle Linn leaf on healing of NSAID-induced experimental ulcer: A novel role of free radical scavenging action. Indian J Exp Biol. 2003;41:311–315.
  20. Adebisi MA, Akomolafe RO. Gastro-protective effect of methanol extract of Vernonia amygdalina leaf on aspirin-induced gastric ulcer in Wistar rats. Toxicology Reports. 2017;4:625–633.
  21. Kuna L, Jakab J, Smolic R, Raguz-Lucic N. Peptic Ulcer Disease: A brief review of conventional therapy and herbal treatment options. J Clin Med. 2019;8(2):17. doi: 10.3390/jcm8020179.
  22. Almadi MA, Lu Y. Peptic ulcer disease. The Lancet. 2024;404(10447):68–81.
  23. Narayanan M, Reddy KM, Marsicano E. Peptic ulcer disease and Helicobacter pylori infection. Mo Med. 2018;115(3):219–224.
  24. ASGE Standards of Practice Committee. Banerjee S, Cash BD, Dominitz JA, et al. The role of endoscopy in the management of patients with peptic ulcer disease. Gastrointest Endosc. 2010;71(4):663–668.
  25. Kawamura N, Ito Y, Sasaki M. Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers. Published November 12, 2013.
  26. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1999;340:1888–1899.
  27. Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: Why doesn’t the stomach digest itself? Physiol Rev. 2008;88:1547–1565.
  28. Fanaroff AC, Roe MT. Contemporary reflections on the safety of long-term aspirin treatment for the secondary prevention of cardiovascular disease. Drug Saf. 2016;39:715–727.
  29. Madhumita M, Guha P, Nag A. Extraction of betel leaves (Piper betle L.) essential oil and its bio-actives identification: Process optimization, GC-MS analysis, and antimicrobial activity. Ind Crops Prod. 2019;138:111578.
  30. Das S, Parida R, Sandeep IS, Nayak S, Mohanty S. Biotechnological intervention in betelvine (Piper betle L.): A review on recent advances and future prospects. Asian Pacific J Trop Med. 2016;9(10):938–946.
  31. Jane NS, Deshmukh AP, Joshi MS. Review of study of different diseases on betelvine plant and control measures. Int J Appl Innov Eng Manag. 2014;3(3):560–563.
  32. Khan AA, Bhatnagar SP, Sinha BN, Lal UR. Pharmacogenetic specifications of eight cultivars of Piper betle from eastern region of India. Pharmacog J. 2013;5(4):176–183.
  33. Pradhan LD, Suri KA, Pradhan DK, Roy PB. Golden heart of nature: Piper betle L. J Pharmacognosy Phytochem. 2013;1(6):147.
  34. Patel NM, Jain DD, Suryawanshi HP, Pawar SP. Phytopharmacological study of Piper betle leaf. PSGVPM’s College of Pharmacy.
  35. Singh T, Singh P, Pandey VK, Singh R, Dar AH. A literature review on bioactive properties of betel leaf (Piper betle L.) and its applications in the food industry.
  36. Mane PP, Rai MP, Thilakchand KR, Bhat HP. The phytochemistry, traditional uses, and pharmacology of Piper betle L. (Betel Leaf): A Pan-Asian medicinal plant. Updated November 20, 2024.
  37. Zumbroich TJ. The origin and diffusion of betel chewing: A synthesis of evidence from South Asia, Southeast Asia, and beyond. eJournal of Indian Medicine. 2007–2008;1:87–140.
  38. “Betel-leaf farming in coastal area.” Dawn. May 13, 2002.

Reference

  1. Debashish Banerjee,Sayanti bhattacharya ,Sandip k.Biochemical Mechanism of Healing Activity of the Natural Phenolic, Allylpyrocatechol Against Indomethacin-Induced Gastric Ulceration in Mice 22 April 2008- Vol. 53, Iss: 11, pp 2868-2877
  2. Pace V. Use of Nonsteroidal anti inflammatory drugs in cancer.Palliat Med 1995; 9:273-286.
  3. Chandra, V., Tripathi, S., Verma, N. K., Singh, D. P., Chaudhary, S. K., & Roshan, A. (2012). Piper betel: Phytochemistry, traditional use & pharmacological activity – A review. International Journal of Pharmaceutical Research and Development (IJPRD), 4(04), 216-223.
  4. Miederer SE. Will anti-ulcer drugs soon differ only in their side effects? Fortschr Med. 1986;104:918–920. [PubMed] [Google Scholar]
  5. Leung, Anna M., Maria J. Redlak, and Thomas A. Miller. "Aspirin-Induced Mucosal Cell Death in Human Gastric Cells: Role of a Caspase-Independent Mechanism." Digestive Diseases and Sciences, vol. 54, no. 1, 2008, pp. 28–35.
  6. Leung, Anna M., Maria J. Redlak, and Thomas A. Miller. "Aspirin-Induced Mucosal Cell Death in Human Gastric Cells: Role of a Caspase-Independent Mechanism." Digestive Diseases and Sciences 54, no. 1 (2008): 28–35.
  7. Madhumita M, Guha P, Nag A. Extraction of betel leaves (Piper betle L.) essential oil and its bio-actives identification: Process optimization, GC-MS analysis and anti-microbial activity. Ind. Crops Prod. 2019;138:111578.
  8. Cronquist A. An Integrated System of Classification of Flowering Plants. Columbia University Press; 1981.
  9. Chattapdayay SP, Maity S. Diseases of Betelvine and Species. ICAR; 1967.
  10. Biswas, P., Anand, U., Chatterjee Saha, S., Kant, N., Mishra, T., Masih, H., Bar, A., Pandey, D. K., Jha, N. K., Majumder, M., & Das, N. (2022). Betelvine (Piper betle L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes. Journal of Cellular and Molecular Medicine, 26(8),
  11. Furukawa Y, Fukazawa N, Miyama Y, Hayashi K, Furukawa S. Stimulatory effect of 4-alkylcatechols and their diacetylated derivatives on the synthesis of nerve growth factor. Biochem Pharmacol. 1990;40(10):2337–2342.
  12. Banerjee, Debashish, et al. "Biochemical Mechanism of Healing Activity of the Natural Phenolic, Allylpyrocatechol Against Indomethacin-Induced Gastric Ulceration in Mice." Digestive Diseases and Sciences, vol. 53, no. 11, 2008, pp. 2868–2877.
  13. Bhattacharya S, Banerjee D, Bauri AK. Healing property of the Piper betel phenol, allyl pyrocatechol against indomethacin-induced stomach ulceration and mechanism of action. World J Gastroenterol. 2007;13(27):3705–3713. doi: 10.3748/wjg.v13.i27.3705.
  14. Pace V. Use of nonsteroidal anti-inflammatory drugs in cancer. Palliat Med. 1995;9:273–286. doi: 10.1177/026921639500900402.
  15. Garner A. Adaptation in the pharmaceutical industry, with particular reference to gastrointestinal drugs and diseases. Scand J Gastroenterol Suppl. 1992;193:83–89. doi: 10.3109/00365529209096011.
  16. Dhikav V, Singh S, Pande S, Chawla A, Anand KS. Non-steroidal drug-induced gastrointestinal toxicity: Mechanisms and management. J Indian Clin Med. 2003;4:315–322.
  17. Miederer SE. Will anti-ulcer drugs soon differ only in their side effects? Fortschr Med. 1986;104:918–920.
  18. Borrelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res. 2000;14:581–591. doi: 10.1002/1099-1573(200012)14:8<581>3.0.co;2-s.
  19. Majumdar B, Ray Chaudhuri SG, Ray A, Bandyopadhyay SK. Effect of ethanol extract of Piper betle Linn leaf on healing of NSAID-induced experimental ulcer: A novel role of free radical scavenging action. Indian J Exp Biol. 2003;41:311–315.
  20. Adebisi MA, Akomolafe RO. Gastro-protective effect of methanol extract of Vernonia amygdalina leaf on aspirin-induced gastric ulcer in Wistar rats. Toxicology Reports. 2017;4:625–633.
  21. Kuna L, Jakab J, Smolic R, Raguz-Lucic N. Peptic Ulcer Disease: A brief review of conventional therapy and herbal treatment options. J Clin Med. 2019;8(2):17. doi: 10.3390/jcm8020179.
  22. Almadi MA, Lu Y. Peptic ulcer disease. The Lancet. 2024;404(10447):68–81.
  23. Narayanan M, Reddy KM, Marsicano E. Peptic ulcer disease and Helicobacter pylori infection. Mo Med. 2018;115(3):219–224.
  24. ASGE Standards of Practice Committee. Banerjee S, Cash BD, Dominitz JA, et al. The role of endoscopy in the management of patients with peptic ulcer disease. Gastrointest Endosc. 2010;71(4):663–668.
  25. Kawamura N, Ito Y, Sasaki M. Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers. Published November 12, 2013.
  26. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1999;340:1888–1899.
  27. Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: Why doesn’t the stomach digest itself? Physiol Rev. 2008;88:1547–1565.
  28. Fanaroff AC, Roe MT. Contemporary reflections on the safety of long-term aspirin treatment for the secondary prevention of cardiovascular disease. Drug Saf. 2016;39:715–727.
  29. Madhumita M, Guha P, Nag A. Extraction of betel leaves (Piper betle L.) essential oil and its bio-actives identification: Process optimization, GC-MS analysis, and antimicrobial activity. Ind Crops Prod. 2019;138:111578.
  30. Das S, Parida R, Sandeep IS, Nayak S, Mohanty S. Biotechnological intervention in betelvine (Piper betle L.): A review on recent advances and future prospects. Asian Pacific J Trop Med. 2016;9(10):938–946.
  31. Jane NS, Deshmukh AP, Joshi MS. Review of study of different diseases on betelvine plant and control measures. Int J Appl Innov Eng Manag. 2014;3(3):560–563.
  32. Khan AA, Bhatnagar SP, Sinha BN, Lal UR. Pharmacogenetic specifications of eight cultivars of Piper betle from eastern region of India. Pharmacog J. 2013;5(4):176–183.
  33. Pradhan LD, Suri KA, Pradhan DK, Roy PB. Golden heart of nature: Piper betle L. J Pharmacognosy Phytochem. 2013;1(6):147.
  34. Patel NM, Jain DD, Suryawanshi HP, Pawar SP. Phytopharmacological study of Piper betle leaf. PSGVPM’s College of Pharmacy.
  35. Singh T, Singh P, Pandey VK, Singh R, Dar AH. A literature review on bioactive properties of betel leaf (Piper betle L.) and its applications in the food industry.
  36. Mane PP, Rai MP, Thilakchand KR, Bhat HP. The phytochemistry, traditional uses, and pharmacology of Piper betle L. (Betel Leaf): A Pan-Asian medicinal plant. Updated November 20, 2024.
  37. Zumbroich TJ. The origin and diffusion of betel chewing: A synthesis of evidence from South Asia, Southeast Asia, and beyond. eJournal of Indian Medicine. 2007–2008;1:87–140.
  38. “Betel-leaf farming in coastal area.” Dawn. May 13, 2002.

Photo
Kirti Pawar
Corresponding author

Dr Uttamrao Mahajan college of pharmacy , chalisgaon ,maharashtra .

Photo
Dipali Suryawanshi
Co-author

Dr Uttamrao Mahajan college of pharmacy , chalisgaon ,maharashtra

Photo
Dhiraj Patil
Co-author

Dr Uttamrao Mahajan college of pharmacy , chalisgaon ,maharashtra

Kirti Pawar*, Dipali Suryawanshi, Dhiraj Patil, Dr. Prakash Sapkale, Biochemical Mechanism of Healing Activity of the Natural Phenolic, Allylpyrocatechol Against Aspirin-Induced Gastric Ulceration, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 2266-2274. https://doi.org/10.5281/zenodo.14748904

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