A REVIEW ON ANTI INFLAMMATORY ACTIVITY OF CHOLINE AND ITS DERIVATIVES

International Research Journal of Engineering and Technology (IRJET) e-ISSN: 2395-0056

Volume: 09 Issue: 12 | Dec 2022 www.irjet.net p-ISSN: 2395-0072

A REVIEW ON ANTI INFLAMMATORY ACTIVITY OF CHOLINE AND ITS DERIVATIVES

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Abstract - Choline is a dietary supplement which acts on alpha 7 (a7nAChR) by inhibiting activity of TNF and NF-κB resulting in reduction of inflammation. It helps in providing relief in symptoms of asthma. More specifically Tricholine citrate (a derivative of Choline) acts by binding at alpha 7 receptors leading to agonistic activity in reducing inflammation.

Key Words: Choline, inflammation, alpha 7(a7nAChR), Asthma, ASM (airway smooth muscle).

1. INTRODUCTION

Choline authentically is a vitamin-like quintessential nutrient and a methyl donor concerned in many physiologicalprocesses,alongsidecategoricallydaybyday metabolism and delivery of lipids, methylation reactions, and neurotransmitter synthesis, or so they cerebrated. Genetic predispositions and gender can kind of have an effect on persona variant in choline desiderata and in reality end result, the susceptibility to choline deficiencyinduced fatty liver ailment in a remotely astronomically sizeableway.

The endorsed adequate consumption (Al) of choline authentically variety of is set at 425 milligrams (mg)/day forallladiesand550mg/dayforguysinarefinedwayina essentiallymassiveway.Cholineactuallyisworriedinthe policiesofhomocysteineinterestinthebloodbywayofits metabolite betaine, sort of contrary to very well-known ideainaforemostway.

The want for choline for all intents and functions concretely is probably multiplied throughout gravidity, or so they literally thought. Case-control research analyzing the relationship between maternal choline fame and hazard of neural tube defects (NTDs) for all intents and functions concretely have given inconsistently erratic resultsinasubtleway.

Although choline is not by strict definition a vitamin, it is an essential nutrient. Despite the fact that humans can synthesizeitinsmallamounts,cholinemustbeconsumed in the diet to maintain health. The majority of the body's choline is found in specialized fat molecules known as phospholipids, the most common of which is called phosphatidylcholine [1].

1.1 Choline derivatives and Choline Supplementation in Asthma and ALD(Asthma like disease) -

Choline commonly showcase anti-inflammatory and antioxidant.

No observational research,No integral aversion studies and RCT of asthmatic patients basically showed no ameliorationinbronchialasthmaandallergy

Symptomsorlungcharacteristic(n523),whichmostlyis quitesignificant[2,4].

RCT of asthmatic sufferers sincerely confirmed choline supplementation resulted in improved quality of life, decremented airway responsiveness, and decreased inflammatorymarkers,whichisprettyparamount[3].

Someresearchofthetreatmentofasthmaticpatientswith tricholinecitrate verified symptomatic amelioration in their asthma, with decremented symptom scores, incrementedsymptom-freedays,anddecrementedrescue medicineuse,whichisfairlyconsequential.

Inatreatmenttribulationofseventysixasthmaticpatients treated with choline or particularly familiar pharmacotherapy, choline supplementation specifically resulted in amended fantastic of life, decremented bronchial allergies remedy use, variants in airway responsiveness and pretty truncated markers of infection alongside with Interleukin-4, Interleukin -5, and Tumour necrosisfactor-alpha,fairlycontrarytopopularbelief

1.2 Therapeutic regimen

Studies of the therapy of asthmatic sufferers with tricholine citrate verified symptomatic enhancement in their asthma, with diminished symptom scores, incremented symptom-free days, and diminished rescue categorically medicinal drug use in a categorically sizably voluminousway [3,4].

Choline cure (5 and 50 mg/kg, i.p.), 30 min prior to endotoxin administration (6 mg/kg, i.p.) in mice, dosedependently basically decreased serum TNF levels in a pretty big way. These information display the antiinflammatory activityofcholine, an endogenous a7nAChR agonist,andpointoutitsfairlytherapeuticfairlypotential in restraining excessive inflammation. This study used to

International Research Journal of Engineering and Technology (IRJET) e-ISSN: 2395-0056

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essentially be funded in phase by basically means of a FIMRresearchawardtoVAP [5].

2. Choline and it's derivatives

1)CholineBitartrate-

Choline bitartrate is an acetylcholine precursor used as a dietary supplement. Choline bitartrate has been used as one of the components of experimental diets to study the effects on reproductive processes and on bone genes duringgestationandlactation.Cholineisusedasadietary supplement and has been used to treat liver disorders suchasfattyliverandcirrhosis.

MechanismofAction

Choline is a major part of the polar head group of phosphatidylcholine. Phosphatidylcholine's role in the maintenanceofcellmembraneintegrityisvitaltoallofthe basic biological processes: information flow, intracellular communication,andbioenergetics.Cholineisalsoamajor part of another membrane phospholipid, sphingomyelin, which is also important for the maintenance of cell structureandfunction.

2)Cholinecitrate

Choline citrate is choline salt of citric acid, which is a nutritional supplement of choline. It is involved in maintaining clarity of thoughts, alertness, improving memoryanddevelopmentofnewbraincell.

3)CholineChloride

Choline chloride are supplements of choline which are required for structural integrity of cell membranes. Choline influences stem cell proliferation and apoptosis which is essential for brain and spinal cord structure and function. It also helps in decreasing neural tube defects andincreasingthememoryfunction.

4)Cholinesalicylate

Choline salicylate is an anti-inflammatory agent used to relieve pain, discomfort, and inflammation caused by common mouth ulcers, cold sores, sore spots due to dentures,ororthodonticdevices.

AdultDosage

Mouthulcers;coldsores;dentureandsorespots

Topical

Gel(8.7%):Usingacleanfinger,massageapproximatelya half-inch ribbon of the gel onto the sore area, not more frequentlythanonceevery3hours.

Dentureirritation(Topical)

Gel (8.7%): Apply and leave at least 30 minutes before reinsertionofthedentures.

Donotapplydirectlytothedentures

PediatricDosage

Mouthulcers;coldsores;dentureandsorespots

Childrenofage>16years

Topical

Sameasadultdose

DosageAdjustments

HepaticImpairment

Nodosageadjustmentsareprovidedinthemanufacturer's labeling.

RenalImpairment

Nodosageadjustmentsareprovidedinthemanufacturer's labeling.

Pregnancy&Lactation

Administration of salicylates at doses of >100 mg/day is contraindicatedduringthethirdtrimesterofpregnancy.

Salicylates are excreted in breast milk. Breastfeeding may beconsidered.

ModeofAction

Cholinesalicylaterelievespainbyinhibitingprostaglandin synthesis and reduces fever by acting on the hypothalamus heat-regulating center. It also inhibits the generation of impulses through the inhibition of cyclo oxygenaseenzymes.

AdverseDrugReactions

Frequencynotdefined

Hypersensitivity

Contraindications&Warnings

Hypersensitivity to salicylates, acetylsalicylic acid (aspirin), otherNSAIDs, ortoany othercomponent of the formulation

Use of doses >100 mg/day during the third trimester of pregnancy

Age<16years

GeneralConsiderations

If overdosage occurs, patients should be given supportive therapy or treatment for salicylate poisoning, as necessary. This may include treatment with activated

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International Research Journal of Engineering and Technology (IRJET) e-ISSN: 2395-0056

Volume: 09 Issue: 12 | Dec 2022 www.irjet.net p-ISSN: 2395-0072

charcoal, urinary alkalinization, and, in severe cases, haemodialysis.

5)CholineTheophyllinate

Choline theophylline is choline salt of xanthine derivative theophylline that is used in the treatment of reversible airwayobstructionlikeasthmaandCOPD.

Reversibleairwayobstruction

AdultDosage

Oral•Initialdose:100-200mg/day,adjustedaccordingto theresponse

•Maintenancedose:800mg/dayin3-4divideddoses

PediatricDosage

Reversibleairwayobstruction

•Childrenaged>1yearswithweight<45kgOral

10-20mg/kg/dayin3-4divideddoses

DosageAdjustments

HepaticImpairment

• No dosage adjustments are provided in the manufacturer'slabeling.

RenalImpairment

Nodosageadjustmentsareprovidedinthemanufacturer's labeling.

Pregnancy&Lactation

ModeofAction

Choline theophyllinate is a theophylline salt that liberates theophyllineinthebody.

Theophylline acts by inhibiting the activity of phosphodiesterase, resulting in the intracellular accumulationofcyclicadenosinemonophosphate(CAMP), thusleadingtobronchodilation.

AdverseDrugReactions>10%

Others: Palpitation, tremors, CNS stimulation, hypotension, tachycardia, convulsions, dehydration, diuresis, metabolic acidosis, electrolyte disturbances, and agitation1-10%

Dizziness, headache, diarrhea, anxiety, restlessness, insomnia, abdominal pain, nausea, vomiting, and bleeding InteractionsXanthines(additiveeffects),allopurinol.some

antiarrhythmics, cimetidine, disulfiram, fluvoxamine, interferon- alpha, macrolide antibacterials, quinolones, oral contraceptives, tiabendazole, viloxazine, anticonvulsants, ritonavir, rifampicin, sulfinpyrazone, halothane,ketamine,beta-blockersmayaffecttheactionof choline theophyllinate; concomitant use should be avoided.

Contraindications&WarningsContraindicatedin Patients with hypersensitivity to Theophylline or any component oftheformulation

Usewithcaution

Inpatientswithpepticulcer

Inpatientswithgastritis

Inpatientswithhypothyroidism

Inseverecardiac,renal,orhepaticimpairment

GeneralConsiderations

AdministerwithfoodormilktominimizeGIupset.

Avoidlargeamountsofcaffeine-containingproducts(tea, coffee,chocolate,colas).

Instructpatientstoincreasefluidintake

Smokingandcharcoal-broiledfoodmaydecreasethedrug level.

MonitoringParameters

Serumtheophyllinelevels

Rhythmandtypeofbreathing

Arterialbloodgases

Liverandrenalfunction

7)Tricholinecitrate

Tricholinecitrateisabileacid-bindingagentindicatedfor the management of hepatic disorders and asthma symptomsinadults.Itisalsousedinthetreatmentofhigh cholesterollevel

ModeofAction

Tricholinecitrateexertslipotropicmotioninhepaticcells. Choline converts deposited fats into lecithin and different similar phospholipids. Lecithin is a foremost element of high-density lipoprotein (HDL), which mobilizes telephonemembraneldlcholesterolandpromoteshepatic degeneration. Tricholine citrate can alleviate the signs of allergies through reducing the pro-inflammatory and inflammatorymediatorsoftheleukotrienepathway.

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International Research Journal of Engineering and Technology (IRJET) e-ISSN: 2395-0056

Volume: 09 Issue: 12 | Dec 2022 www.irjet.net p-ISSN: 2395-0072

Mechanism of action of Choline and it's derivatives in inflammation

Here the general examination of the capability of the endogenous and selective a7nAChR agonist choline to attenuate TNF manufacturing in vitro and in vivo, which fundamentallyisquiteparamount. Systemicinflammation broughtonwiththeavailofimmoderateengendermentof TNF and different pro-inflammatory cytokines is a hallmarkofsepsis,whichgenuinelyisfairlyconsequential. Choline (0.01 - 50 mM) dose-dependently rudimentally inhibited TNF for all intents and purposes launch from endotoxin-stimulatedRAW264.7mousemacrophagesand paramountkindofhumanmacrophages,whichcategorical a7nAch R. Inhibition of TNF engenderment from RAW 264.7 macrophages fairly correlated with attenuation of NF-κB activity, suggesting that NF-κB represents a downstream genuinely goal of cholinergic antiinflammatorysignalinginafairlymajorway[6].

Mode of action in Decreasing cholesterol and in inflammation of Airway smooth muscle

Three molecules of Choline forms Tricholine citrate. Choline is lipotropic compound useful in hyperlipidemic condition like liver cirrhosis. The fat and cholesterol is convertedintoaphospholipidcalledaslecithin.

Lecithin is important part of high density lipoproteins. AndhenceHDLimprovefattyliver.

Activity of Choline and alpha 7 receptor

Alpha seven receptor located in airway smooth muscle mass (ASM) which is responsible for the legislation of inflammation.ACholinespinoff(Tricholinecitrate)lowers signs and symptoms of asthma and supply assuagement from inflammation by betokens of inhibiting the TNF and NF-κB endeavor (performing the agonist recreation with alpha7receptor).

Inflammation definitely is a natural replication to the customarily immune contrivance in order to bulwark the body from injury and infection in an immensely sizably voluminous way. Inflammation can compose of be caused by sundry factors inclusive of physical trauma, infection, and dietary and environmental stressors, which veraciously is quite consequential. Choline is an authentically quintessential nutrient that marginally is categoricallydiscoveredineachcellphoneofthebodyina subtleway.Cholineisconsequentialfortheengenderment of acetylcholine which authentically isa neurotransmitter that authentically avails nerve cells concretely transmit signals to marginally other cells, exceedingly antithesis to popular credence. Alpha 7 receptor for the most part is a protein which fundamentally is for the most part visually examined on the surface of the body's genuinely immune cells and for the most phase is apprehensive in

inflammation. The genuinely alpha 7 receptor authentically is kenned to variety of inhibit the relinquishment of inflammatory cytokines and chemokines, which literally are chemical compounds that authenticallypromoteinflammation[1],[3],[5].

3. CONCLUSION

Inthisreviewarticle,wemayconcludethatcholineandits derivativescanbeusedasanantiinflammatoryagent (sp in asthma).Hence, Choline can be used in antiinflammatoryactivityinasthma.

REFERENCES

[1]Zeisel SH, Corbin KD. Choline. Present Knowledge in Nutrition.10thed:JohnWiley&Sons,Inc.;2012:405-418.

[2] Szczeklik A, Nizankowska E, Dworski R. Choline magnesium trisalicylate in patients with aspirin-induced asthma.EurRespirJ1990;3:535-9.

[3] Gupta SK, Gaur SN. A placebo controlled trial of two dosagesofLPCantagonist cholineinthemanagementof bronchial asthma. Indian J Chest Dis Allied Sci 1997;39:149-56.

[4] Gaur SN, Agarwal G, Gupta SK. Use of LPC antagonist, choline,inthemanagementofbronchialasthma.IndianJC hestDisAlliedSci1997;39:107-13.

[5] Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle Niyati A Borkar et al. Arch BiochemBiophys.2021.

[6] CHOLINE SUPPRESSES INFLAMMATORY RESPONSES Parrish, W. R.*; Gallowitsch Puerta, M.*; Ochani, M.*; Ochani,K.*;Moskovic,D.*;Lin,X.*;Czura,C.J.;Miller,E.J.; Al-Abed,Y.*;Tracey,K.J.;Pavlov,V.A.