Sains Malaysiana 54(12)(2025): 2925-2936

http://doi.org/10.17576/jsm-2025-5412-11

 

Southeast Asian Medicinal Plants in Osteoporosis: A Systematic Review of Anti-Osteoclastogenesis in Preclinical Models

 (Tumbuhan Ubatan Asia Tenggara untuk Osteoporosis: Ulasan Sistematik Anti-Osteoklastogenesis dalam Model Praklinikal)

 

INTAN ZARINA ZAINOL ABIDIN^1,*, YAMUNA SILVARAJA¹ & SHAHRUL HISHAM ZAINAL ARIFFIN²

 

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

²Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

 

Received: 7 August 2025/Accepted: 19 November 2025

 

Abstract

Osteoporosis is a chronic metabolic bone disorder characterised by excessive osteoclast-mediated bone resorption and compromised bone microarchitecture, especially following estrogen deficiency in postmenopausal women. Despite the availability of antiosteoporosis drugs, long-term use is limited by adverse effects, initiating the rise of research and development in plant-derived bioactive. Southeast Asia is rich in medicinal plants with reported antioxidant and estrogenic properties that may modulate bone remodelling. This systematic review aims to investigate the molecular and histomorphometric effects of Southeast Asian plant extracts on osteoblast activity and bone integrity in in vivo models of postmenopausal osteoporosis. This preclinical study followed PRISMA 2020 guidelines and was conducted through a systematic search of PubMed, Scopus, and ScienceDirect from 2014-2024. An extensive search was conducted across these three databases, yielding 546 articles. Sixteen articles of in vivo studies using an ovariectomized or postmenopausal rat models were included based on defined eligibility criteria. Risk of bias was assessed using SYRCLE’s tool.  A systematic review of 16 in vivo studies, involving 13 plant species, demonstrated consistent improvements in trabecular structure, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th). Plant extracts such as Bixa orellana L. (Annatto) and Marantodes pumilumvar. alata (Kacip Fatimah) demonstrated improvement in anti-osteoclastogenesis activity by modulating signaling pathways involving RANKL, NFATc1, NF-kB, reactive oxygen species (ROS), and estrogen receptor alpha (ERα). Several compounds also enhanced osteoblast activity and bone mineral density. In conclusion, Southeast Asian plant extracts demonstrate multi-target bone-protective effects and represent promising candidates for future anti-osteoporotic therapies.

Keywords: Bone resorption; medicinal plants; osteoporosis; phytoestrogens; RANKL 

 

Abstrak

Osteoporosis merupakan gangguan metabolik tulang kronik yang dicirikan oleh aktiviti osteoklas berlebihan, mengakibatkan peningkatan penyerapan tulang serta kemerosotan mikroarkitektur tulang, terutamanya disebabkan kekurangan estrogen dalam kalangan wanita pascamenopaus. Walaupun ubat antiosteoporosis tersedia, penggunaannya dalam jangka panjang adalah terhad akibat kesan sampingan, sekali gus mendorong penyelidikan dan pembangunan bioaktif berasaskan tumbuhan. Asia Tenggara kaya dengan tumbuhan ubatan yang dilaporkan mempunyai sifat antioksidan dan estrogen yang berpotensi memodulasi pembentukan semula tulang. Ulasan sistematik ini bertujuan untuk menilai kesan molekul dan histomorfometrik ekstrak tumbuhan Asia Tenggara terhadap aktiviti osteoblas dan integriti tulang dalam model in vivo osteoporosis pascamenopaus. Kajian praklinikal ini mengikuti garis panduan PRISMA 2020 dan dijalankan melalui carian sistematik dalam pangkalan data PubMed, Scopus dan ScienceDirect bagi tempoh 2014-2024. Carian menyeluruh daripada tiga pangkalan data menghasilkan sejumlah 546 artikel. Sebanyak 16 artikel kajian in vivo menggunakan model tikus ovariektomi atau pascamenopaus dipilih berdasarkan kriteria kelayakan yang ditetapkan. Risiko berat sebelah dinilai menggunakan alat SYRCLE. Ulasan sistematik terhadap 16 kajian in vivo melibatkan 13 spesies tumbuhan menunjukkan peningkatan yang konsisten dalam struktur trabekular, termasukketumpatan mineral tulang (BMD), isi padu tulang/isi padu tisu (BV/TV), bilangan trabekular (Tb.N) dan ketebalan trabekular (Tb.Th). Ekstrak tumbuhan seperti Bixa orellana L. (Annatto) dan Marantodes pumilum var. alata (Kacip Fatimah) menunjukkan aktiviti anti-osteoklastogenesis melalui pengawalaturan tapak jalan isyarat yang melibatkan RANKL, NFATc1, NF-κB, spesies oksigen reaktif (ROS) dan reseptor estrogen alfa (ERα). Beberapa sebatian juga didapati meningkatkan aktiviti osteoblas dan ketumpatan mineral tulang. Kesimpulannya, ekstrak tumbuhan Asia Tenggara menunjukkan kesan pelindung tulang pelbagai sasaran dan berpotensi untuk dijadikan calon terapi antiosteoporosis pada masa hadapan.

Kata kunci: Fitoestrogen; osteoporosis; penyerapan tulang; RANKL; tumbuhan ubatan

 

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*Corresponding author; email: intanzarina@cyberjaya.edu.my