Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists
The roots and rhizomes of have long been used as folk medicine in Asia and usually named as "Zhizhuxiang" in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Ca...
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Veröffentlicht in: | Frontiers in pharmacology 2018-08, Vol.9, p.885-885 |
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Sprache: | eng |
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Zusammenfassung: | The roots and rhizomes of
have long been used as folk medicine in Asia and usually named as "Zhizhuxiang" in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Ca
2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of
and its EtOAc,
-BuOH and H
O soluble parts (0.01 mg/ml, respectively) were tested herein on Ca
2.2, using whole-oocyte recordings
by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Ca
2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (
-
). All isolates were then sent for further bioactive verification (
and
at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds
and
were tested on various ion channels including Ca
1.2, Ca
2.1 and Ca
3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound
and
(an abundant compound) inhibited Ca
2.2 with an EC
of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Ca
1.2, Ca
2.1 and Ca
3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds
and
appear to act as allosteric modulators rather than pore blockers of Ca
2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of
for relieving the abdominal distention and pain may mediate through Ca
2.2 channel. Our work is the first demonstration of inhibition of Ca
2.2 by iridoids, which may provide a fresh source for finding new analgesics. |
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ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2018.00885 |