Title:Anti-neuropathic Pain Mechanistic Study on A. conyzoides Essential Oil,
Precocene II, Caryophyllene, or Longifolene as Single Agents and in
Combination with Pregabalin
Volume: 22
Issue: 6
Author(s): Y. Purwandi Sukmawan, Kusnandar Anggadiredja and I. Ketut Adnyana*
Affiliation:
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institut Teknologi Bandung, Bandung,
West Java, 40116, Indonesia
Keywords:
A. conyzoides, caryophyllene, essential oil, longifolene, precocene II, neuropathic pain.
Abstract:
Background: Neuropathic pain has become a contributor to the global burden of illness.
However, the currently available drugs exhibit inadequate pain relief and significant side effects. Our
previous study demonstrated that the essential oil of Ageratum conyzoides exerts potent antineuropathic
pain activity through opioid receptor activation. Precocene II, longifolene, and caryophyllene
are the largest component of the A. conyzoides essential oil.
Objective: The objective of the study was to determine the anti-neuropathic pain activity of precocene
II, longifolene, and caryophyllene as single agents and in combination with pregabalin. Possible
mechanisms of action involving the opioid receptor, ATP-sensitive potassium channel, and gammaaminobutyric
acid (GABA) were further investigated.
Methods: The experimental animals (male mice Swiss Webster) were divided randomly into seven
groups, namely, Normal control (naïve mice), Negative control (CMC 1%), Sham (CMC 1%), Positive
control (Pregabalin 0,195 mg/ 20 g BW of mice), Test I (Precocene II 21.09 mg/Kg BW), Test II
(Longifolene 9.94 mg/Kg BW), and Test III (Caryophyllene 3.64 mg/Kg BW). Each group contained
3 animals. The test groups that demonstrated anti-neuropathic pain activity were further tested in combination
with pregabalin, followed by mechanistic studies. The negative, positive, and test I-III groups
were induced with chronic constriction injury.
Results: The results of the study demonstrated that caryophyllene and longifolene, but not precocene
II, exerted anti-neuropathic pain activity. The caryophyllene was shown to involve in the activation of
opioid receptors and ATP-sensitive potassium channels. It was also reported to increase GABA concentration
in the spinal cord. We further found that longifolene exerted its action via opioid receptor
activation. The combination of A. conyzoides essential oil, longifolene, or caryophyllene with pregabalin
demonstrated additive anti-neuropathic pain activity.
Conclusion: Taken together, the results of the present study suggested that the A. conyzoides essential
oil and caryophyllene have the potential to be developed as novel drugs to treat neuropathic pain.
