Rehmannia alcohol extract alleviates osteoarthritis pain in rats by reducing secretion of pain-related neuropeptides CGRP and substance P while protecting cartilage from degradation.
CGRP and substance P both reducedRehmannia extract decreased secretion of both key pain neuropeptides while simultaneously protecting cartilage and reversing brain changes visible on fMRI.
What the researchers found
Rehmannia alcohol extract and its active component Rehmannioside D delayed cartilage degradation and reduced inflammation in osteoarthritis rats. The extract significantly reduced secretion of calcitonin gene-related peptide (CGRP) and substance P (SP) — two neuropeptides central to pain signaling. Functional MRI revealed that the treatment reversed pathological changes in the cerebral cortex and hippocampus, indicating the extract influences brain pain processing regions in addition to its local anti-inflammatory effects at the joint.
Why it matters
Osteoarthritis pain affects hundreds of millions of people, and current treatments often have significant side effects with long-term use. Understanding that Rehmannia works by reducing pain neuropeptides like CGRP and substance P — the same targets as modern migraine drugs — could lead to new approaches for OA pain management. The dual mechanism of cartilage protection plus neuropeptide modulation is particularly interesting.
How the study worked
The study combined in vivo (rat osteoarthritis model) and in vitro experiments. Therapeutic effects were assessed through cartilage degradation markers, inflammatory markers, and measurement of CGRP and substance P secretion levels. Functional magnetic resonance imaging (fMRI) was used to evaluate changes in brain activity in pain-related regions. The active ingredient Rehmannioside D was also tested separately to identify the compound responsible for the effects.
What this study cannot tell us
This is an animal study using rat osteoarthritis models, and the results may not directly translate to humans. The abstract does not provide specific quantitative data for the neuropeptide reductions or cartilage protection metrics. The dosing, duration, and route of administration in rats may not correspond to practical human dosing. As a herbal extract, standardization and quality control present additional challenges for clinical translation.
How to read the evidence
This is a preclinical animal study using rat osteoarthritis models. While it provides mechanistic insight and identifies a promising pathway, the evidence cannot be directly applied to human patients without clinical trials.
When this study was published
Published in 2023, this is recent research that connects traditional herbal medicine with contemporary neuropeptide pain biology.
The bigger picture
CGRP and substance P are among the most important pain-signaling neuropeptides in the body, and drugs targeting CGRP have already transformed migraine treatment. This study suggests these same neuropeptide pathways play a role in osteoarthritis pain and can be modulated by a natural plant extract. It connects traditional herbal medicine to modern neuropeptide biology, potentially opening new therapeutic strategies for chronic joint pain.
Questions still open
- Would Rehmannia extract or Rehmannioside D reduce CGRP and substance P levels in human osteoarthritis patients?
- How does the magnitude of neuropeptide reduction compare to established CGRP-targeting drugs?
- Could Rehmannioside D be developed as a standardized pharmaceutical rather than an herbal extract?
Common questions
What are CGRP and substance P, and why do they matter for pain?
Is Rehmannia extract available as a treatment for osteoarthritis?
Read the original research
Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection.
Heliyon, 9(9), e19322
Citation
Huang, Yanfeng; Lin, Qing; Tan, Xue; Jia, Liangliang; Li, Hui; Zhu, Zaishi; Fu, Changlong; Wang, Lili; Liu, Linlong; Mao, Min; Yi, Zhouping; Ma, Dezun; Li, Xihai. (2023). Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection.. Heliyon, 9(9), e19322. https://doi.org/10.1016/j.heliyon.2023.e19322