Sains Malaysiana 54(8)(2025): 1875-1887

http://doi.org/10.17576/jsm-2025-5408-01

 

Osteogenic Potential in Piper sarmentosum Roxb.: A Systematic Review of in vitro and in vivo Evidence

(Potensi Osteogenik Piper sarmentosum Roxb.: Tinjauan Sistematik Pembuktian secara in vitro dan in vivo)

 

INTAN ZARINA ZAINOL ABIDIN1,*, ROA M.A. ALIWAISI2, ZULHAM YAMAMOTO3, MUHAMMAD DAIN YAZID4 & SHAHRUL HISHAM ZAINAL ARIFFIN5

 

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Cyberjaya, 63000 Cyberjaya, Selangor, Malaysia

2Graduate Research School, University of Cyberjaya, 63000 Cyberjaya, Selangor, Malaysia

3Department of Histology, Faculty of Medicine, Universitas Sumatera Utara, Medan,

20155 North Sumatra, Indonesia

4Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia

5Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

 

Received: 14 March 2025/Accepted: 26 June 2025

 

Abstract

Piper sarmentosum Roxb. (Ps) has various therapeutic properties, however, the in vitro and in vivo effects on bone health, suitable dosage, and involvement of key metabolites remain unclear. This systematic review aims to evaluate Ps role in bone formation, dosage considerations, and active metabolites, highlighting the potential in future bone health therapy. The search was conducted in PubMed (Medline), Scopus, and Web of Science databases from 2014-2025. Related original articles published in English were included, while duplicates, secondary, and unrelated sources were excluded. Six articles from 1,523 met the inclusion criteria, and two additional eligible articles were manually selected from the reference lists, bringing the total to eight articles. Four studies used in vivo glucocorticoid-induced osteoporotic Sprague-Dawley rat models, while one employed an in vivo zebrafish model. The in vitro study involved two human Peripheral Blood Stem Cells and one MC3T3-E1 cell-line. The articles showed osteoprotective effects, particularly in glucocorticoid-induced models. Leaf extracts improved bone microstructure and osteoblast activity both in vitro and in vivo, evidenced by increased OPG mRNA expression, reduced RANKL/OPG mRNA expression ratio, enhanced mineralization, upregulation of osteoblast gene markers, and antioxidant activity with asarone and gamma-asarone as potential metabolites. Ps extract promotes osteoblast differentiation and bone formation in vitro and in vivo. In vivo effective dosage is 125 mg/kg/day in rats and 100-400 µg/mL in zebrafish, while 1-50 µg/mL for in vitro. Metabolites such as asarone and gamma-asarone need further investigation to clarify their role in bone health.

Keywords: Bone formation; metabolites; osteoblast differentiation; osteogenic; Piper sarmentosum Roxb.

 

Abstrak

Piper sarmentosumRoxb. (Ps) mempunyai pelbagai sifat terapeutik, namun kesannya terhadap kesihatan tulang secara in vitro dan in vivo, dos optimum serta metabolit utama masih belum jelas. Penyelidikan ini bertujuan menilai peranan Ps dalam pembentukan tulang, dos yang sesuai dan metabolit aktif yang berpotensi untuk rawatan kesihatan tulang pada masa hadapan. Pencarian pangkalan data PubMed (Medline), Scopus dan Web of Science dilakukan pada 2014-2025. Artikel asal berkaitan diterbitkan dalam Bahasa Inggeris telah dikenal pasti, manakala artikel bertindan, sumber sekunder dan tidak berkaitan diasingkan. Enam daripada 1,523 artikel memenuhi kriteria kemasukan, manakala dua artikel tambahan dipilih secara manual daripada senarai rujukan, memberikan keseluruhan lapan artikel. Secara in vivo, empat artikel menggunakan tikus Sprague-Dawley osteoporosis teraruh glukokortikoid, manakala satu kajian melibatkan ikan zebra. Kajian in vitro pula melibatkan dua artikel sel stem darah periferi dan satu artikel titisan sel MC3T3-E1. Kesemua artikel menunjukkan kesan pelindung tulang terutamanya dalam model in vivo teraruh glukortikoid. Ekstrak daun telah menambahbaik struktur mikro-tulang dan aktiviti osteoblas secara in vitro dan in vivo melalui peningkatan pengekspresan mRNA OPG, penurunan nisbah pengekspresan mRNA RANKL/OPG, peningkatan mineralisasi dan pengawalaturan penanda gen osteoblas dan aktiviti antioksidan serta kehadiran asaron dan asaron-gamma sebagai metabolit berpotensi untuk rawatan kesihatan tulang. Ekstrak Ps mengaruh pembezaan osteoblas dan pembentukan tulang secara in vitro dan in vivo. Dos berkesan bagi in vivo adalah 125 mg/kg/hari (tikus) dan 100-400 µg/mL (ikan zebra), manakala 1-50 µg/mL pula untuk kajian in vitro. Metabolit seperti asaron dan asaron-gamma memerlukan kajian lanjutan bagi mengenal pasti peranannya dalam kesihatan tulang.  

Kata kunci: Metabolit; osteogenik; pembentukan tulang; pembezaan osteoblas; Piper sarmentosum Roxb.

 

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*Corresponding author; email: izzarina7@gmail.com

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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