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Addiction Research; Addiction Therapy; Addiction; Anti-inflammatory activity; Malvastrum tricuspidatum; Carrageenan; Indomethacin

Introduction

Inflammation is a localised defensive response of mammalian tissues towards allergic or chemical irritation, damage, and infection [1]. Inflammation is characterized by pain, redness, heat, and swelling [2]. Increased levels of endogenous biological substances such as nitric oxide, reactive oxygen species, prostaglandin E2, and cytokines are linked to the development of inflammation. [1] Increased vascular permeability, protein denaturation and membrane modification are all concerned with inflammation. [3] Cyclooxygenase (COX) is a key enzyme in the synthesis of prostacyclins, prostaglandins, and thromboxanes, all of which are involved in inflammation, pain, and platelet aggregation. Vasoactive compounds enhance the permeability of arterioles, allowing blood cells, chemical substances, blood proteins, and fluid to accumulate in that location. This fluid buildup causes swelling and can be painful because it compresses nerves in the region. Prostaglandins may also produce nerve irritation and contribute to pain [4]. Uncontrolled inflammatory reactions may have a role in the onset and development of inflammatory disorders such as atherosclerosis, rheumatoid arthritis, cardiovascular disease, and cancer [5]. In addition to these diseases prostatitis, anaphylaxis, diabetes, chronic renal disease, digestive disorders, alzheimer's disease, bacterial infections, and new corona virus infection are all linked with inflammation, particularly at the cellular level, which can lead to major health issues [6]. Inflammatory free radicals assault biomembranes and macromolecules, exacerbating inflammatory consequences. Furthermore, free radicals such as peroxyl and hydroxyl are extremely reactive molecules that include charged nitrogen and oxygen ions, causing oxidative stress if not well controlled. Antioxidants are utilized to prevent oxidative stress by scavenging free radicals and protecting tissues from oxidative damage. However, synthetic antioxidants such as propyl gallate, butylated hydroxytoluene, and butylated hydroxyanisole have been linked to carcinogenicity, hepatotoxicity, and other undesirable effects in patients, as well as being more labile and inaccessible that limiting their utility. As a result, antioxidant supplements derived from natural sources such as herbs and fruits provide a feasible alternative for combating oxidative stress in the body, particularly during inflammation[7]. Herbal medicines have been used for a long time to prevent and treat disorders, including inflammation. Many people are now use herbal treatments in their daily lives as Phytonutrients or nutraceuticals, and the usage of herbal pharmaceuticals and Phytonutrients or nutraceuticals is spreading quickly over the world. According to the World Health Organization (WHO), three-quarters of people get their daily healthcare from traditional and plant-based medicine. Herbal medications are becoming increasingly popular since they have fewer adverse effects than synthetic pharmaceuticals [8]. A wide range of plants have been employed for medicinal reasons throughout antiquity. Most plant components have been extracted and may have anti-inflammatory and antioxidant qualities. Use of plant extract can protect against chronic inflammation by down regulating inflammatory mediators. Plant bioactive principles can also modulate oxidative stress [9]. The active phytochemical elements of herbal formulations or medications, such as alkaloids, flavonoids, terpenoids, phenols, polyphenols, tannins, saponins, polysaccharides, proteins, lipids, and peptides, are responsible for their pharmacological activity [10]. Malvastrum Tricuspidatum (Malvaceae family) is also known as False mallow or kharenti [11]. Malvastrone is found in the leaves of Malvastrum Tricuspidatum. Phenylethylamine, dotriacontane, dotriacontanol, sitosterol, stigmasterol, campesterol, lutein, N-methylphenylethylamine, and an unidentified indole alkaloid are found in the aerial portions[12]. Palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, malvalic acid, and sterculic acid are also found in the plant. Malvastrum Tricuspidatum has several therapeutic benefits, including the application of the leaves to inflamed sores and wounds, the administration of a plant decoction in dysentery, and the use of the flowers in cough, chest, and lung disorders. Malvastrum Tricuspidatum is used as an anti-inflammatory, analgesic and in the treatment of jaundice and ulcers as mentioned in traditional Indian system of medicine [11]. Numerous tribal tribes throughout the world use various components of this plant. The crushed leaves of this plant, along with salt or alcohol, are used by Mexican Kickapoo Indians to treat ringworm infection. The Bhil tribes of Rajasthan use a decoction of this herb to treat jaundice. This plant's leaf infusion is used to treat diabetes in Mexico. Pharmacological testing revealed that this plant has antinociceptive, analgesic, and antibacterial properties [13, 14]. As mentioned in the Indian traditional system of medicines that plant possesses anti-inflammatory activity but not proved scientifically so in the present study we evaluate anti-inflammatory activity of plant Malvastrum Tricuspidatum by using invivo animal models to justify its traditional use in experimental animals (Figures 1 and 2).

Figure 1: Various inducers of inflammation.

Figure 2: Effect of aqueous extract of plant on carrageenan induced paw edema in rats.

Source: AEMT - Aqueous extract of Malvastrum Tricuspidatum.

Materials and Methods

Plant

Fresh leaves of plant Malvastrum Tricuspidatum were procured from Maharashtra and were authenticated. The voucher specimens were submitted and preserved as Institute Herbarium Nos: LORDS/2022/ PCOG/08 Herbarium sample was also preserved.

Animals

The study used healthy Wistar albino male rats weighing between 150 and 200 gram. They were kept in temperature-controlled circumstances (22-30oC), with a relative humidity of at least 30% but no more than 70%. (Other than during room cleaning). According to OECD Guideline 423, lighting was artificial with 12 hour light and 12 hour dark cycles. All animals received a standard pellet diet and water. The present work was carried out with a prior permission by IAEC of Lords University with CSPSEA registration number 1386/PO/Re/S/10/ CPCSEA.

Chemicals

All substances necessary to assess anti-inflammatory activity were acquired at Jaipur local market and are of standard grade.

Aqueous leaf extraction of Malvastrum Tricuspidatum

Malvastrum Tricuspidatum aqueous leaf extraction: We obtained aqueous extract of Malvastrum Tricuspidatum using the Soxhlet equipment with hot continuous extraction technique. The dry and powdered medication was packaged. The Soxhlet device is a continuous, automated process that does not require any more operation. This procedure is not time-consuming, as the extraction period for a standard-sized sample is 48 hours. The extract was refrigerated until further investigation [15].

Phytochemical Characterization

Aqueous extract were subjected to general phytochemical analysis for the presence of carbohydrates, proteins, amino acids, tannins, phenolic flavonoids, alkaloids, anthraquinone, glycosides, saponins, and steroidal nucleus using the standard methods [16-18].

In- vivo anti-inflammatory activity

Carrageenan was formed as 1 percent W/V solution in 0.9 percent saline no more than 24 hours before use. The lambda form does not gel at room temperature and is injectable to elicit an inflammatory reaction. The protocol was followed for performing an anti-inflammation experiment in inflamed rodents generated by carrageenan.

Procedure

Paw edema was produced by injecting 0.1 ml of 1% w/v carrageenan suspended in 1% CMC into the sub-plantar tissues of each rat's left hind paw. The rats were put into four groups of six animals each. Group I Carrageenan as the control, Group II Aqueous extract (200 mg/kg), Group III Aqueous extract (400 mg/kg), and Group IV Indomethacin (10 mg/kg) as the standard reference. The paw volume was determined by immersing the foot in the plethysmograph mercury bath before injecting the carrageenan, as well as after 1, 2, 3, and 4 hours. The anti-inflammatory activity was measured as a percentage reduction of oedema in animals administered with the extract under test versus a carrageenan control group. Food was withheld from 12 hours before medication delivery till the trial was completed. Following a 60-minute injection of 0.1 ml of 1 percent w/v carrageenan into the subplantar area of the left paw, the test and control drug were administered [19,20]. Immediately following carrageenan injection in both the control and other treatment groups (Vt). The percentage of inhibition for each group was calculated using the formula.

Where Vc and Vt represent average Paw volume of control and treatment animal respectively [21].

Statistical analysis

After submitting the data gathered from numerous investigations, the results were interpreted. Graph pad Prism 9.0.2 was used for statistical analysis, which comprised one-way ANOVA followed by tests such as Dunnett and t-test. P<0.05 is deemed statistically significant.

Result

Phytochemical investigation shows that aqueous extract of plant Malvastrum Tricuspidatum known to possess Carbohydrate, steroids, flavonoids, tannins and glycosides. Paw volume of various treated group at 1, 2, 3, and 4hr and their % inhibition are tabulated in Table 1, result shows that aqueous extract at dose 200mg/kg and 400mg/kg shows 30.68 % and 45.45 % inhibition in paw volume respectively. Standard drug indomethacin (10mg/kg) shows 67.80 % inhibition in paw volume. Result obtained was statistically significant (p˂0.05).

Table 1: Effect of aqueous extract of plant Malvastrum Tricuspidatum on carrageenan induced paw edema in rats.

Discussion

Inflammation is a process of the organism's immunological defence in reaction to an external (burn, infection, allergy, trauma) or endogenous (infection, allergy, trauma) aggression (cancer cells or autoimmune pathologies). Inflammation is defined at the tissue level by redness, swelling, heat, discomfort, and loss of tissue function as a result of local immunological, vascular, and inflammatory cell responses to infection or damage. Vascular permeability alterations, leukocyte recruitment and accumulation, and inflammatory mediator release are all important microcirculatory processes that occur throughout the inflammatory phase [22]. The aim of the inflammatory response is the prevention and elimination of the infecting agents from the organism, reparation of damaged tissues and prevention of further disease development. Although many factors can trigger the inflammation, the mechanisms of the immune system response are generally common for all of them [23]. Chronic inflammation is the important cause of many chronic illnesses, including autoimmune diseases, allergies, metabolic syndrome, cardiovascular dysfunction, and cancer [24]. Acute inflammation progresses in two stages the first phase begins with the release of histamine, serotonin, and kinins. The second phase is associated with the production of prostaglandinlike compounds within 2-3 hours. The second phase is responsive to both steroidal and nonsteroidal anti-inflammatory agents that are therapeutically beneficial. Prostaglandins are the primary cause of acute inflammation. Carrageenan is a powerful molecule that promotes the production of inflammatory and proinflammatory mediators [25]. Many anti-inflammatory treatments, including as corticosteroids and nonsteroidal anti-inflammatory medicines, are available to treat this, however these synthetic agents have side effects such as GIT damage, gastric erosions, and, in extreme cases, serious bleeding and death [26]. In addition to anti-inflammatory effect, NSAIDs also have antipyretic and analgesic properties. These medications inhibit COXs enzymes, which are rate-determining enzymes for prostaglandins and other prostanoids synthesis [27]. Plants are the primary source of compounds used in the creation of new medications [28]. Several studies have been conducted in order to identify natural bioactive compounds with anti-inflammatory properties. Secondary metabolites of medicinal plants, such as polyphenols, flavonoids, terpenoids, and alkaloids, are important sources for anti-inflammatory drug development. According to recent research, these molecules give anti-inflammatory properties by suppressing inflammatory mediators involved in inflammatory processes, such as cytokines, chemokines, and pro and neo-inflammatory mediators [29,30]. According to the study, aqueous extract of the plant Malvastrum Tricuspidatum contains a variety of phytoconstituents such as steroids, flavonoids, tannins, and glycosides etc. Table 1 shows that drug extracts at 200 mg/kg and 400 mg/kg enhance the percent inhibition in paw volume by 30.68% and 45.45%, respectively. This might account for the anti-inflammatory action of aqueous extracts at the given dosage.

Conclusion

Our findings indicate that Malvastrum Tricuspidatum has significant antiinflammatory efficacy. More research into the separation of the bioactive chemical compound of the plant Malvastrum Tricuspidatum, as well as research into biochemical pathways, may result in the creation of an effective anti-inflammatory medicine with minimal toxicity.

Acknowledgement

Providing research facility from faculty of Pharmacy, Lords University, Alwar is gratefully acknowledged.

Conflict of Interest

Nil

1. Sinnasse P, Tereno S (2017) . Ann Med Psychol 175: 370-375.

, ,

2. Untas A, Aguirrezabal M, Chauveau P, Leguen E, Combe C, et al. (2009) . Néphrologie Thérapeutique 5: 193-200.

, ,

3. Hser YI, Mooney LJ, Huang D, Zhu Y, Tomko RL, et al. (2017) . J Subst Abuse Treat 81: 53-58.

, ,

4. Stern AF (2014) . Occup Med 64: 393-394.

, ,

5. Duquette J,Hospital Anxiety and Depression Scale(HADS) (2015) . Centre de recherche CRIR-site INLB, CISSS de la Montérégie-Centre, Sapin.
6. Vallieres EF, Vallerand RJ (1990) . Int JPsychol 25: 305-316.

, ,

7. Walburg V, Laconi S, Van Leeuwen N, Chabrol H (2014) . Enfance Adolesc 62: 163-167.

, ,

8. García JA, Olmos FC, Matheu ML, Carreño TP (2019) . Heliyon 5: e01378.

, ,

9. Aluja A, Rolland JP, García LF, Rossier J (2007) . J PersAssess 88: 246‑249.

, ,

10. De Aquino JP, Sherif M, Radhakrishnan R, Cahill JD, Ranganathan M, et al. (2018) . Clin Ther 40: 1448-1456.

, ,

11. Karila L, Roux P, Rolland B, Benyamina A, Reynaud M, et al. (2014) . Curr Pharmaceutical Design 20: 4112‑4118.

, ,

12. Guillem E, Pelissolo A, Vorspan F, Bouchez-Arbabzadeh S, Lépine JP (2009) . L’Encéphale 35: 226-233.

, ,

13. Guillem E, Arbabzadeh-Bouchez S, Vorspan F, Bellivier F (2015) . L’Encéphale 41: S7-S12.

, ,

14. Dugas EN, Sylvestre MP, Ewusi-Boisvert E, Chaiton M, Montreuil A, et al. (2019) . Can J Psychiatry 64: 329-337.

, ,

15. Sideli L, Quigley H, La Cascia C, Murray RM (2020) . JDual Diagn 16: 22-42.

, ,

16. Glowacz F, Schmits E (2017) . Eur Rev Soc Psychol 67: 171-179.

,

17. Stapinski LA, Montgomery AA, Araya R (2016) . Drug Alcohol Depend166: 109-115.

, ,

18. Roberts B (2019) . West JEM 20: 557-572.

, ,

19. Blanco C, Hasin DS, Wall MM, Flórez-Salamanca L, Hoertel N, et al. (2016) . JAMA Psychiatry 73: 388-395.

, ,

20. Esmaeelzadeh S, Moraros J, Thorpe L, Bird Y (2018) . Neuropsychiatr Dis Treat 14: 3241-3251.

, ,

21. P (2006) . 1: 121-135.
22. Leadbeater BJ, Ames ME, Linden-Carmichael AN (2019) . Addiction 114: 278-293.

, ,

23. Hengartner MP, Angst J, Ajdacic-Gross V, Rossler W (2020) . J AffectDisord 272: 98-103.

,

24. Gage SH, Hickman M, Heron J, Munafò MR, Lewis G, et al. (2015) . PLoS ONE 10: e0122896.

, ,

25. Halladay JE, MacKillop J, Munn C, Jack SM, Georgiades K (2020) . J Addict Nurs 31: 92-101.

, ,

26. Danielsson AK, Lundin A, Agardh E, Allebeck P, Forsell Y (2016) . J Affect Disord 193: 103-108.

, ,

27. Delforterie MJ, Lynskey MT, Huizink AC, Creemers HE, Grant JD, et al. (2015) . DrugAlcohol Depend150: 98-104.

, ,

28. Duperrouzel J, Hawes SW, Lopez-Quintero C, Pacheco-Colón I, Comer J, et al. (2018) . AddictBehav 78: 107-113.

, ,

29. Leweke FM, Koethe D (2008) . Addict Biol 13: 264-275.

, ,

30. Wild LG, Flisher AJ, Bhana A, Lombard C (2004) . J ChildPsycholPsychiatry45: 1454-1467.

, ,