Physalis angulata Linn. As a Potential Liver Antifibrotic Agent In Rats.

Muhammad Begawan Bestari(1), Enny Rohmawaty(2), Aziiz Mardanarian Rosdianto(3), Hermin A. Usman(4), Winda A. M. Saragih(5), Ade Zuhrotun(6), Rini Hendriani(7), Yoga Windhu Wardhana(8), Savira Ekawardhani(9), Hesti Lina Wiraswati(10), Nenny Agustanti(11), Sumartini Dewi(12), Muhammad Palar Wijaya(13),


(1) Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital, Bandung
(2) Division of Pharmacology and Therapy, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung
(3) Veterinary Medicine Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung
(4) Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran, Bandung
(5) Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung
(6) Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung
(7) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung
(8) Study Center of Pharmaceutical Dosage Development, Department of Pharmaceutics and Pharmaceuticals Technology, Faculty of Pharmacy, Universitas Padjadjaran, Bandung
(9) Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung
(10) Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung
(11) Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital, Bandung
(12) Immunology Study Center, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung
(13) Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital, Bandung
Corresponding Author

Abstract


Background: No drug with a liver antifibrotic effect for treating non-alcoholic fatty liver disease (NAFLD) has been approved. Physalis angulata Linn., better known to Indonesian as ciplukan, has natural abilities in various metabolic and inflammatory diseases. This study aims to determine the effect of ethyl acetate fraction of P. angulata in the NAFLD rat model by examining alanine aminotransferase (ALT), cholesterol levels, and liver histopathological features, which are methods to evaluate the course of the disease and the potential antifibrotic effect.

Method: This research is an in vivo study on male Wistar rats conducted at the Animal Laboratory, Faculty of Medicine, Universitas Padjadjaran, from September to November 2020. Rats were grouped randomly into seven groups of 5 each. The NAFLD models were created by giving a diet containing 20% margarine for four weeks. The intervention groups were given vitamin E, ethyl acetate fraction of P. angulata, and both combinations. The statistical analysis examined differences in each group based on their histopathological features, ALT, and cholesterol levels.

Results: Histopathological results in the group given P. angulata at a dose of 0.32 mg resembled normal liver, and the ALT level was similar to vitamin E. The administration of P. angulata at 0.16 mg dose improved cholesterol levels.

Conclusions: P. angulata ethyl acetate fraction at a dose of 0.32 mg improved the histopathological and serum ALT levels in the NAFLD rat model, which could be the basis for the mechanism of P. angulata's antifibrotic ability in NAFLD conditions.


Keywords


antifibrotic; ciplukan; fibrosis; NAFLD; Physalis angulata

References


Marchesini G, Day CP, Dufour JF, Canbay A, Nobili V, Ratziu

V, et al. EASL-EASD-EASO Clinical Practice Guidelines

for the management of non-alcoholic fatty liver disease. J

Hepatol [Internet]. 2016;64(6):1388–402. Available from:

http://dx.doi.org/10.1016/j.jhep.2015.11.004 doi: 10.1016/j.

jhep.2015.11.004

Li J, Zou B, Yeo YH, Feng Y, Xie X, Lee DH, et al.

Prevalence, incidence, and outcome of non-alcoholic fatty

liver disease in Asia, 1999–2019: a systematic review and

meta-analysis. Lancet Gastroenterol Hepatol [Internet].

;4(5):389–98. Available from: http://dx.doi.org/10.1016/

S2468-1253(19)30039-1 doi: 10.1016/S2468-1253(19)30039-

Delli Bovi AP, Marciano F, Mandato C, Siano MA, Savoia M,

Vajro P. Oxidative Stress in Non-alcoholic Fatty Liver Disease.

An Updated Mini Review. Front Med. 2021;8(February):1–14.

https://doi.org/10.3389/fmed.2021.595371

Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit

pathogenesis of non-alcoholic fatty liver disease (NAFLD).

Metabolism [Internet]. 2016;65(8):1038–48. Available

from: http://dx.doi.org/10.1016/j.metabol.2015.12.012 doi:

1016/j.metabol.2015.12.012

Longhi R, Almeida RF, Machado L, Duarte MMMF, Souza

DG, Machado P, et al. Effect of a trans fatty acid-enriched

diet on biochemical and inflammatory parameters in Wistar

rats. Eur J Nutr. 2017;56(3):1003–16. https://doi.org/10.1007/

s00394-015-1148-y

Aydos LR, Amaral LA Do, Souza RS de, Jacobowski AC,

Santos EF Dos, Macedo MLR. Nonalcoholic fatty liver

disease induced by high-fat diet in C57BL/6 models. Nutrients.

;11(12):1–12. https://doi.org/10.3390/nu11123067

Van Herck MA, Vonghia L, Francque SM. Animal models of

nonalcoholic fatty liver disease—a starter’s guide. Nutrients.

;9(10):1–13. https://doi.org/10.3390/nu9101072

Dhibi M, Brahmi F, Mnari A, Houas Z, Chargui I, Bchir L,

et al. The intake of high fat diet with different trans fatty acid

levels differentially induces oxidative stress and non alcoholic

fatty liver disease (NAFLD) in rats. Nutr Metab. 2011;8:1–12.

https://doi.org/10.1186/1743-7075-8-65

Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L.

Current guidelines for the management of non-alcoholic

fatty liver disease: A systematic review with comparative

analysis. World J Gastroenterol [Internet]. 2018/08/14.

;24(30):3361–73. Available from: https://www.ncbi.nlm.

nih.gov/pubmed/30122876 doi: 10.3748/wjg.v24.i30.3361

Rinella M, Tacke F, Sanyal A, Anstee Q. Report on the

AASLD/ EASL joint workshop on clinical trial endpoints in

NAFLD. J Hepatol. 2019;71:823–833.

Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal

AJ. Mechanisms of NAFLD development and therapeutic

strategies. Nat Med [Internet]. 2018;24(7):908–22. Available

from: http://dx.doi.org/10.1038/s41591-018-0104-9 doi:

1038/s41591-018-0104-9

Sanyal A, Chalasani N, Kowdley K, McCullough A, Diehl

A, Bass N, et al. Pioglitazone, vitamin E, or placebo for

nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–

Bril F, Biernacki DM, Kalavalapalli S, Lomonaco R,

Subbarayan SK, Lai J, et al. Role of Vitamin E for nonalcoholic

steatohepatitis in patients with type 2 diabetes: A randomized

controlled trial. Diabetes Care. 2019;42(8):1481–8. https://

doi.org/10.2337/dc19-0167

Choi E-M, Hwang J-K. Investigations of anti-inflammatory

and antinociceptive activities of Piper cubeba, Physalis

angulata and Rosa hybrida. J Ethnopharmacol [Internet].

;89(1):171–5. Available from: http://www.sciencedirect.

com/science/article/pii/S0378874103002800 doi: https://doi.

org/10.1016/S0378-8741(03)00280-0

Yang Y-J, Yi L, Wang Q, Xie B-B, Dong Y, Sha C-W.

Anti-inflammatory effects of physalin E from Physalis

angulata on lipopolysaccharide-stimulated RAW 264.7 cells

through inhibition of NF-κB pathway. Immunopharmacol

Immunotoxicol [Internet]. 2017;39(2):74–9. Available

from: https://doi.org/10.1080/08923973.2017.1282514 doi:

1080/08923973.2017.1282514

Rohmawaty E, Rosdianto AM, Usman HA, Saragih WAM,

Zuhrotun A, Hendriani R, et al. Antifibrotic effect of the ethyl

acetate fraction of ciplukan (Physalis angulata Linn.) in rat liver

fibrosis induced by CCI4. J Appl Pharm Sci. 2021;11(12):175–

https://doi.org/10.7324/JAPS.2021.1101217

Dewi S, Isbagio H, Purwaningsih EH, Kertia N, Setiabudy

R, Setiati S. A Double-blind, Randomized Controlled Trial of

Ciplukan (Physalis angulata Linn) Extract on Skin Fibrosis,

Inflammatory, Immunology, and Fibrosis Biomarkers in

Scleroderma Patients. Acta Med Indones. 2019;51(4):303–10.

Kusumaningtyas R, Laily N, Limandha P. Potential of

Ciplukan (Physalis Angulata L.) as Source of Functional

Ingredient. Procedia Chem [Internet]. 2015;14:367–72.

Available from: http://www.sciencedirect.com/science/

article/pii/S1876619615000510 doi: https://doi.org/10.1016/j.

proche.2015.03.050

Mahalaksmi A, Nidavani R. Physalis angulata L. An

Ethnopharmacological review. Indo Am J Pharm Res.

;4(3):1479-1486.

Guillaumie F, Justesen SFL, Mutenda KE, Roepstorff

P, Jensen KJ, Thomas ORT. Fractionation, solid-phase

immobilization and chemical degradation of long pectin

oligogalacturonides. Initial steps towards sequencing of

oligosaccharides. Carbohydr Res. 2006;341(1):118–29.

https://doi.org/10.1016/j.carres.2005.10.011

Pincus MR, Tierno PM, Gleeson E, Bowne WB. Evaluation

of Liver Function. In: Henry’s Clinical Diagnosis and

Management by Laboratory Methods. 23rd ed. Elsevier Inc.;

p. 295–6.

Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline:

Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol

[Internet]. 2017;112(1):18–35. Available from: http://dx.doi.

org/10.1038/ajg.2016.517 doi: 10.1038/ajg.2016.517

Singh AS, Masuku MB. SAMPLING TECHNIQUES &

DETERMINATION OF SAMPLE SIZE IN APPLIED

STATISTICS RESEARCH: AN OVERVIEW. Int j Econ

Commer Manag. 2014;II(11):1–22.

Albrecht M, Henke J, Tacke S, Markert M, Guth B. Effects

of isoflurane, ketamine-xylazine and a combination of

medetomidine, midazolam and fentanyl on physiological

variables continuously measured by telemetry in Wistar rats.

BMC Vet Res. 2014;10(1):1–14. https://doi.org/10.1186/

s12917-014-0198-3

El Hadi H, Vettor R, Rossato M. Vitamin E as a treatment for

nonalcoholic fatty liver disease: Reality or myth? Antioxidants.

;7(1). https://doi.org/10.3390/antiox7010012

Caldwell S, Ikura Y, Dias D, Isomoto K, Yabu A, Moskaluk

C, et al. Hepatocellular Ballooning in NASH Stephen. J

Hepatol. 2011;53(4):719–23. https://doi.org/10.1016/j.

jhep.2010.04.031.Hepatocellular

Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich

T, et al. Long-term follow- up of patients with nonalcoholic

fatty liver. Clin Gastroenterol Hepatol. 2009;7:234–8.

Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA,

Boparai N YZ. Pathological features associated with fibrosis

in nonalcoholic fatty liver disease. Hum Pathol. 2004;35:196–

Carotti S, Vespasiani-Gentilucci U, Perrone G, Picardi A,

Morini S. Portal inflammation during NAFLD is frequent and

associated with the early phases of putative hepatic progenitor

cell activation. J Clin Pathol. 2015;68(11):883–90. https://doi.

org/10.1136/jclinpath-2014-202717

Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE,

Lavine JE, et al. Portal Chronic Inflammation in Nonalcoholic

Fatty Liver Disease. Hepatology. 2009;49(3):809–20. https://

doi.org/10.1002/hep.22724.Portal

Kim KH, Lee M-S. Pathogenesis of Nonalcoholic

Steatohepatitis and Hormone-Based Therapeutic Approaches.

Front Endocrinol (Lausanne) [Internet]. 2018;9(485).

Available from: https://www.frontiersin.org/article/10.3389/

fendo.2018.00485 doi: 10.3389/fendo.2018.00485

Soares MBP, Bellintani MC, Ribeiro IM, Tomassini TCB,

Ribeiro dos Santos R. Inhibition of macrophage activation

and lipopolysaccaride-induced death by seco-steroids

purified from Physalis angulata L. Eur J Pharmacol

[Internet]. 2003;459(1):107–12. Available from: http://www.

sciencedirect.com/science/article/pii/S0014299902028297

doi: https://doi.org/10.1016/S0014-2999(02)02829-7

Czauderna C, Castven D, Mahn F, Marquardt J. Context-

Dependent Role of NF- κ B Signaling in Primary Liver Cancer

Volume 24, Number 3, December 2023 215

Physalis angulata Linn. As a Potential Liver Antifibrotic Agent In Rats

— from Tumor Development to Therapeutic Implications.

Cancers (Basel). 2019;11(8):1053. https://doi.org/https://doi.

org/10.3390/cancers11081053

Porika RP, Lunavath V, Mamidala E. Preliminary

phytochemical investigation and TLC analysis of Physalis

angulata fruit extract. J Pharm Bio Sci. 2014;9(2):11–4.

Martín-Fernández M, Arroyo V, Carnicero C, Sigüenza R,

Busta R, Mora N, et al. Role of Oxidative Stress and Lipid

Peroxidation in the Pathophysiology of NAFLD. Antioxidants.

;11(11):2217. https://doi.org/10.3390/antiox11112217

Ioannou GN. The role of cholesterol in the pathogenesis of

NASH. Trends Endocrinol Metab. 2016;27(2):84–95.

Ioannou G, Subramanian S, Chait A, Haigh W, Yeh M,

Farrell G, et al. Cholesterol crystallization within hepatocyte

lipid droplets and its role in murine NASH. J Lipid Res.

;58:1067–79.

Bieghs V, Hendrikx T, van Gorp P, Verheyen F, Guichot

Y, Walenbergh S, et al. The cholesterol derivative

-hydroxycholesterol reduces steatohepatitis in mice.

Gastroenterology. 2013;144:167–78.

Tirosh O. Hypoxic signaling and cholesterol lipotoxicity

in fatty liver disease progression. Oxid Med Cell Longev.

;2018:2548154.

Tomita K, Teratani T, Suzuki T, Shimizu M, Sato H, Narimatsu

K, et al. Acyl-CoA:cholesterol acyltransferase 1 mediates liver

fibrosis by regulating free cholesterol accumulation in hepatic

stellate cells. J Hepatol. 2014;61:98– 106.

Permatasari N, Kumala YR, Sulakso T. Efek ekstrak daun

ciplukan (Physalis minima L.) terhadap kadar malondialdehid

tulang mandibula tikus (Rattus norvegicus) wistar pasca

ovariektomi. Prodenta J Densitry. 2017;1(1):35–46.

Krishna M, Vadluri R, Kumar EM. In Vitro Determination of

Antioxidant activity of Physalis angulata Linn. Int J Pharma

Bio Sci. 2013;


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