ACTIVE CONSTITUENTS FROM MEDICINAL PLANTS USED  IN INFLAMMATION

Lattupally Varalakshm, Gandhi Archana, Gali Havissu, Gandikota Tarun, Gogada Abhilash, Chinnawar Vaishnavi,

doi:10.5281/zenodo.18409451

Review Paper | Open Access
Volume 04 | Issue 01 | Article Id IJPS/260401346

ACTIVE CONSTITUENTS FROM MEDICINAL PLANTS USED IN INFLAMMATION
Lattupally Varalakshm* Gandhi Archana Gali Havissu Gandikota Tarun Gogada Abhilash Chinnawar Vaishnavi
Holy Mary Institute Of Technology & Science (College Of Pharmacy) Bogaram(v), Keesara (m), Medchal (Dist) 501 301, Telangana, India

Abstract

Medicinal plants are safe and more affordable to treat various diseases, many people depend on medicinal plants to treat inflammation. Inflammation is acute or chronic, which can damange healthy cells lead to diseases.Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds.Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-?B, MAPK, and JAK-STAT pathways. Here. The aim of review is to provide active constituents such as warifterine, berberine, eugenol, andrographolide etc obtained from medicinal plants are used to treat inflammatio

Keywords

Medicinal plants, Inflammation, Active constituents

Introduction

Medicinal plants are generally considered more affordable, safer, and more accessible than synthetic medicine, they have historically served as useful therapeutic agents in ethnomedicine. According to the World Health Organization (WHO), more than 80% of the world’s population still relies on traditional medicines obtained from plants to meet their basic medical needs. plant extracts contain various phytoconstituents (e.g., alkaloids, polyphenols, flavonoids, and terpinoids).they have been demonstrated to exert their activities by interacting simultaneously with numerous biological targets, there by increasing their therapeutic potential.⁽¹⁾1 Medicinal plants are regarded as rich resources of traditional medicines and many of modern medicine are produced from these plants. Medicinal plants have been used to treat various disorders for thousands of years, to add flavor and conserve food and to prevent diseases epidemics. Medicinal plants have been playing an essential role in the development of human culture.⁽²⁾Inflammation is a biological response of the immune system, can be triggered by various factors such as pathogens , damaged cells and toxic compounds.⁽³⁾

The inflammation process is characterized by five cardinal signs: (i) rubor (redness, attributed to hyperemia); (ii) tumor (swelling due to the increase in the permeability of the microvasculature and leakage of protein into the interstitial space); (iii) color (heat related to an increase in blood flow caused by the metabolic activity of the cellular inflammation mediators); (iv) dolor (pain, attributed to changes in the per vasculature and nerve endings); and (v) function lease (dysfunction of the involved organs).⁽⁴⁾Inflammation is two types such as Acute Inflammation and Chronic Inflammation. Acute inflammation is of short duration and its duration is from minutes to few days. The main characteristics are: a) Exudation of fluids b) Plasma protein (edema) c) Emigration of leukocytes specially neutrophils. Chronic inflammation is having longer duration than acute inflammation. It is associated histologically with the presence of lymphocytes, macrophages, proliferation of blood vessels, fibrosis, and tissue necrosis. It is followed by acute inflammation and it starts from the low grade, smoldering asymptomatic response. It may also arise due to the persistent infection by certain organisms such as tubercle bacilli or Treponema pallidum, prolonged exposure to highly toxic agents, either exogenous like silica or endogenous like plasma lipid component resulting into atherosclerosis, autoimmune like rheumatoid arthritis. Acute inflammation response is the initial response after the infection or trauma. It is non- specific in nature and is the first line of defense of body after the danger In acute inflammation, there is increased level of copper, decreased level of zinc. There is occurrence of leukocytosis, thrombocytosis, negative nitrogen balance, increased BMR, increased lipogenesis and lipolysis. There is decrease in plasma protein level, increased C reactive protein level.⁽⁵⁾

Mediators and Biomarkers of InflammationThe discovery of cellular and molecular inflammatory mediators and the development of sensitive biomarkers have rapidly advanced our understanding of inflammation and its role in pathology. Key biomarkers include: Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS),Formation of DNA adducts, Cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha(TNF-α), and chemokines, Acute-phase proteins, such as C-reactive protein or CRP, Prostaglandins, Cyclooxygenase (COX)-related metabolites, Inflammation-related growth factors and transcription factors, such as NF-kappaB, Major immune cell types.⁽⁶⁾The inflammation can be triggered by various pathogens (viruses, bacteria) toxins, toxic compounds, tissue injury. These harmful stimuli initiate a chemical signaling cascade, activating leukocytes, that then produce and release inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α (TNF-α). These cytokines interact with and activate receptors (IL-6R, TNFR-1, TNFR-2, TLR4, GM-CSFR etc.). Receptor activation triggers the phosphorylation of various signaling molecules such as mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), Janus kinase (Jak), resulting in the activation of various transcription factors.⁽⁷⁾

MATERIALS AND METHODS

Medicinal plants have been used since ancient times to treat various diseases, particularly inflammation. This review provides information on active constituents obtained from medicinal plants, Active constituents includes alkaloids (Berberine, Warifteine,aviceninesA-F), glycosides(Dardanols), terpinoids (βMyrcene, Limonene, Andrographolide),polyphenols(Curcumin),phenylpropanoid(eugenol).complexflavonoid glycoside(Quercetin3methoxy4′glucosyl7glucoside),phytosteroids(guggulosterone),Other constituents includes 2-hydroxy-4 methoxybenzaldehyde,Tris(2,4-di-tert-butylphenyl) phosphate. \These active constituents are effective in the treatment of inflammation.

RESULTS AND DISCUSSION

Active constituent: Berberine^(8,9)

Plant name: Coptis chinensis and Hydrastis canadensis

Family : Berberidaceae

It is an isoquinoline alkaloid

Berberine

Berberine has been found to modulate and/or suppress inflammation through suppressing the production of TNF?α, IL?6 and MCP?1, down?regulating the expression of cyclooxygenase?2 (COX?2), reducing generation of PGE2 and formation of exudates, and inhibiting the expression of MMP?2 and MMP?9 through nuclear factor?kB (NF?kB) and mitogen?activated protein kinase (MAPK) signalling cascades.

Active constituent: Warifteine^(10,11)

Plant name: Cissampelos sympodialis

Family: Menispermaceae

It is a bisbenzylisoquinoline alkaloid

Warifteine

Warifteine reduces inflammation by blocking key immune pathways: it inhibits leukocyte migration (like eosinophils & neutrophils), cuts down on pro-inflammatory mediators (like eotaxin, leukotrienes, nitric oxide), reduces allergic responses by lowering IgE and mast cell activation, and modulates cytokines (boosting anti-inflammatory IL-10, reducing pro-inflammatory IL-4/5/13).

Active constituent: β-Myrcene^(12,13) (7-methyl-3-methylene-1,6-octadiene)

plant name: cannabis sativa, Humulus lupulus

family: cannabaceae

It is a monoterpene

β-Myrcene

Myrcene EOs can inhibit the production of pro-inflammatory cytokines, NO, IL-4, and IFN-γ in LPS induced inflammation in the rat Subsequently, myrcene also showed significant anti-inflammatory activity by inhibiting 5-lipoxygenase activity and inhibiting pro-inflammatory cytokines.

Active constituent:Dardanols A–E^(14,15,16)

Plant name: Mandevilla dardanoi

Family:Apocynaceae

It is a new pregnane steroidal glycosides (dardanols A–E)

New pregnane glycosids

Dardanols A, B, C and E showed anti-inflammatory potential by inhibiting the production of nitric oxide and reducing the pro-inflammatory cytokines IL-1β and TNF-α in stimulated macrophages.

Active constituent: Limonene^(17,18)

Plant name: Citrus aurantium, citrus sinensis

Family : Rutaceae It is a monoterpene

Limonene

It act by reduction of the expression of proinflammatory cytokines such as TNF-α, IL1, and IL-6, regulation of iNOS, COX-2, PGE2.

Active constituent: Guggulsterone^(19,20)

Plant name : Commiphora wightii

Family : Burseraceae

It contains Guggulsterone(phytosteroid)

Guggulsterone

This sterol can inhibit NF-κB activation and downregulate the expression of inflammatory gene products such as COX-2 and MMP-9, which are major players in the development of arthritis. We also showed recently that guggulsterone can suppress osteoclastogenesis induced by RANKL (receptor activator of NF-κB ligand), a bone-resorbing cytokine.

Active constituent:Eugenol^(21,22) (4-allyl-2-methoxyphenol)

Plant name : Eugenia caryophyllata (clove)

Family : Myrtaceous

It is a phenylpropanoid

Eugenol (4-allyl-2-methoxyphenol

It is also known to be an inhibitor of pro-inflammatory mediators, including IL-1β and IL-6, tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), expression of inducible oxide nitrate synthase (iNOS) and expression of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and leukotriene C4 and 5-lipoxygenase (5-LOX) [31]. Its anti-inflammatory activity is associated with preventing neutrophil/macrophage chemotaxis and inhibiting the synthesis of inflammatory neurotransmitters, such as prostaglandins and leukotrienes; in addition, eugenol dimers have shown chemopreventive properties by inhibiting cytokine expression in macrophages.

Active constituent :2-hydroxy-4-methoxybenzaldehyde^(23,24)

Plant name : Hemidesmus indicus

Family: Apocynaceae

coumarinolignoids such as hemidesmine

2-hydroxy-4-methoxybenzaldehyde

remarkable suppression of pro-inflammatory markers interleukin-6, macrophage inflammatory protein-1, tumor necrosis factor-α (IL-6, MIP-1, TNF-α).

Active constituent: quarcetin-3 methoxy-4-glucosyl-7-glucoside⁽²⁵⁾

Plant name : Melothria heterophylla

family: Cucurbitaceae

It is a complex flavonoid glycoside

quercetin-3-methoxy-4′-glucosyl-7-glucoside

Inhibits prostaglandin production,. It reduced the amount of arachidonic acid transformed to PGs by suppressing COX-1and cox-2 but suppressing COX-2 level more effectively in comparison to COX1.

Active constituent :Curcumin^(26,27)

plant name: Curcuma longa

Family: Zingiberaceae

Curcumin is a polyphenol, is known chemically as1,7-bis (4-hydroxy-3-methoxyphenyl) −1,6-heptadiene-3,5-dione

Curcumin

Anti-inflammatory effects mainly by inhibiting the activation of nuclear factor-κB (NF-κB) signaling pathway, regulating the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) phosphorylation cascade, and regulating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. and the NLRP3 inflammasome.

Active constituent: Tris(2,4-di-tert-butylphenyl) phosphate^(28,29)

Plant name :Vitex negundo

Family: Verbenaceae

Tris(2,4-di-tert-butylphenyl) phosphate

It inhibits secretory phospholipase A₂ (sPLA₂) enzymes

Active constituent: Andrographolide⁽³⁰⁾

Plant name: Andrographis paniculata

Family:Acanthaceae

Andrographolide is a complex diterpenoid lactone

Andrographolide

Multy -target anti inflammatory agent by inhibiting key pathways like nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase/confluent serine/threonine kinase (PI3K/Akt), mitogen-activated-protein kinase (MAPK), Janus kinase (JAK)/signal transduction and activation of transcription factor (STAT) pathways, as well as other signaling cascades.

SUMMARY AND CONCLUSION

Medicinal plants have huge demand since olden days to treat diseases, active constituensts present in the plants are essential to cure many diseases, every active constituent in the medicinal plants have particular activity, active phytochemicals such as flavonoids, alkaloids, and terpenoids,phytosteroids. These compounds inhibits key inflammatory pathways—NF?κB, COX enzymes, and cytokines (TNF?α, IL?6)—thereby suppressing chronic inflammation activie constituents have anti inflammatory activity such as beriberine obtained from plant coptis chinenesis and hydrastis canadensis, warifterine from cissampelos sympodialis, β-Myrcene obtained from cannabis sativa,Dardanols A–E from Mandevilla dardanoi, Limonene isolated from Citrus aurantium and citrus sinensis, Guggulu obtained from Commiphora wightii, Eugenol isolated from Eugenia caryophyllata(clove), 2-hydroxy-4-methoxybenzaldehyde from Hemidesmus indicus, Quarcetin-3 methoxy-4-glucosyl-7-glucoside isolated from Melothria heterophylla, Curcumin from Curcuma longa, Tris(2,4-di-tert-butylphenyl) phosphate from Vitex negundo, Andrographolide fromAndrographis paniculata. These active constiruents are plays important role to treat inflmmation. Further research and clinical validation of these plant?derived agents could lead to novel, natural drug development strategies for inflammation?related diseases.

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Ricardo C. Calhelha1,2,*,Hala Haddad 1,2,Lúcia Ribeiro 1,2,Sandrina A. Heleno 1,2,Márcio Carocho 1,2 andLillian Barros 1,2.,Inflammation: What’s There and What’s New?., Applied Sciences. 2023, 13(4).
Jagrati Chaurasia*1 , Aayush Agrawal1 , Vivek Gautam1 ,Brijesh Mishra1 , Rama Shukla2 , Sonal Gupta2.,A Review Study about Inflammation, Types and Treatment.,international journal of pharmacy and pharmaceutical research.,March 2020 Vol.:17, Issue:4.
Muhammad Zubair1; Bracken Burns2.,Pathology, Inflammation.,National library of medicine., August 11, 2024.
Anna L Kiss ^1,*.,Inflammation in Focus: The Beginning and the End.,National library of medicine.,Pathol Oncol Res,2022 Jan 4;27.
Zheng Li ¹, Ya-Na Geng ¹, Jian-Dong Jiang ^2,*, Wei-Jia Kong ^1,*.,Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus.,Evid Based Complement Alternat Med. 2014 Feb 11;2014
Seyed?Morteza Ehteshamfar ¹, Masoume Akhbari ², Jalil Tavakol Afshari ¹, Motahareh Seyedi ³, Banafsheh Nikfar ⁴, Abbas Shapouri?Moghaddam ^1,^?, Erfan Ghanbarzadeh^5,,AmirAbbas Momtazi?Borojeni^6.,Anti?inflammatory and immune?modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation.,national library ofmedicine., J Cell Mol Med. 2020 Nov 1;24(23).
H.F. Costa a, C.R. Bezerra-Santos a, J.M. Barbosa Filho a, M.A. Martins b, M.R. Piuvezam a.,Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals.,International Immunopharmacology Volume 8, Issue 4, April 2008, Pages 519-525
Thaline F A Lima ¹, Juliana D B Rocha ¹, Anderson B Guimarães-Costa ¹, José M Barbosa-Filho ², Débora Decoté-Ricardo ³, Elvira M Saraiva ¹, Luciana B Arruda ⁴, Marcia R Piuvezam ², Ligia M T Peçanha ^1,*.,Warifteine, an Alkaloid Purified from Cissampelos sympodialis, Inhibits Neutrophil Migration In Vitro and In Vivo.,J Immunol Res, 2014 Jun 5;2014.
Shelini Surendran ^1,*, Fatimah Qassadi ^2,3, Geyan Surendran ^4,*, Dash Lilley ⁴, Michael Heinrich ^2,3.,Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent?.,National library of medicine., Front Nutr. 2021 Jul 19.
Vishal Tyagi a, Vijay Kumar Singh a, Pramod Kumar Sharma a, Veena Singh b.,Essential oil-based nanostructures for inflammation and rheumatoid arthritis.,Journal of Drug Delivery Science and Technology Volume 60, December 2020.
Francisca S. V. LinsFrancisca S. V. Lins 1,Thalisson A. de Souza 1,Luiza C. F. Opretzka 2,Joanda P. R. e Silva 1,Laiane C. O.Pereira 1,Lucas S. Abreu 3,Anderson A. V. Pinheiro1,George L. D. dos Santos 1,Yuri M. do Nascimento 1,José Iranildo Miranda de
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DanielleAyrTavaresdeAlmeida a 1, SuellenIaraGuirra Rosa a 2, ThaisCamposDias daCruza3,EduardaPavana4,Amílcar SabinoDamazo a 5, IlsamarMendes Soares b 6, Sérgio Donizeti Ascêncio b 7, Antonio Macho a 8, Domingos Tabajara de Oliveira Martins a 9., Mandevilla longiflora (Desf.) Pichon improves airway inflammation in a murine model of allergic asthma.,Journal of Ethnopharmacology Volume 200, 22 March 2017, Pages 51-59.
IlsamarMendes Soares b 6, Sérgio Donizeti Ascêncio b 7, Antonio Macho a 8, Domingos Tabajara de Oliveira Martins a 9., Mandevilla longiflora (Desf.) Pichon improves airway inflammation in a murine model of allergic asthma.,Journal of Ethnopharmacology Volume 200, 22 March 2017, Pages 51-59.
Lujain Bader Eddin ¹, Niraj Kumar Jha ², M F Nagoor Meeran ¹, Kavindra Kumar Kesari ^3,4, Rami Beiram ¹, Shreesh Ojha ^1,*.,.,Neuroprotective Potential of Limonene and Limonene Containing Natural Products,.national library of medicine Molecules. 2021 Jul 27;26(15)
Hossein Maghsoudi1? , Enayatollah Yazadanpanah2.,Evaluation of the Anti-Inflammatory Properties of D-limonene Com.,J Bas Res Med Sci. 2023; 10(1) :1-14.
1)Dinesh Khanna 1 2 3, Gautam Sethi 4, Kwang Seok Ahn 4, Manoj K Pandey 4,AjaikumarB Kunnumakkara 4, Bokyung Sung 4, Amita Aggarwal 5,Bharat B Aggarwal 4.,Natural products as a gold mine for arthritistreatment.,Current Opinion in Pharmacology Volume 7, Issue 3, June 2007, Pages 344-351.
Bhagyasree B, Mruthunjaya K* , Paramakrishnan N, Suresh J.,Guggul – A Treasure of Chemical Constituents,.,International Journal of Pharmacognosy and Phytochemical Research 2019; 11(2);49-
1)Muhammad Farrukh Nisar ^1,2, Mahnoor Khadim ², Muhammad Rafiq ², Jinyin Chen ^1,3, Yali Yang ^4,^?, Chunpeng Craig Wan ^1.,Pharmacological Properties and Health Benefits of Eugenol: A Comprehensive Review,. national library of medicine .,Oxid Med Cell Longev. 2021 Aug 3;2021
Magdalena Ulanowska andBeata Olas., Biological Properties and Prospects for the Application of Eugenol—A Review.,Int. J. Mol. Sci. 2021, 22(7).
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Lattupally Varalakshm

Corresponding author

Holy Mary Institute Of Technology & Science (College Of Pharmacy) Bogaram(v), Keesara (m), Medchal (Dist) 501301.Telangana, India