Incarvillea sinensis - ingredients and uses.

[izo]

next plant profile:

Incarvillea sinensis - Wikipedia

en.wikipedia.org

this seems of the an active principle in this plant:

Incarvillateine - Wikipedia

en.wikipedia.org

 

[izo]

2019 - Natural product incarvillateine aggravates epileptic seizures by inhibiting GABAA currents

A natural monoterpene alkaloid incarvillateine isolated from the plant Incarvillea sinensis is
known to relieve inflammatory and neuropathic pain. However, the molecular target for the
action of incarvillateine remains elusive. Here, we report that incarvillateine exacerbates
epileptic seizures by inhibiting subtypes of γ-Aminobutyric acid type A (GABAA) receptors.
Two-electrode voltage clamp recordings of α1β3γ2, α2β3γ2, α3β3γ2 and α5β3γ2 subtypes
expressed in Xenopus oocytes revealed that incarvillateine inhibited the GABAA currents with
IC50 of 25.1 μM, 43.1 μM , 105.1 μM and 93.7 μM, respectively. Whole-cell patch clamp
recordings of hippocampal slices confirmed that incarvillateine inhibited spontaneous
inhibitory postsynaptic currents (IPSCs), and miniature IPSCs and tonic currents. Moreover,
inhibition of GABAA currents and spontaneous IPSCs by incarvillateine persisted even in the
presence of blockers of adenosine receptors. In addition, incarvillateine enhanced epileptic
discharges induced by Mg2+-free artificial cerebrospinal fluid (ACSF) in hippocampal slices.
Furthermore, intracerebral ventricular injections of incarvillateine increased the severity of
seizures induced by kainic acid in a dose-dependent manner. Taken together, our data
demonstrate that incarvillateine aggravates seizures by inhibition of GABAA currents and
GABAergic synaptic transmissions.

 

[izo]

2005 - A Monoterpene Alkaloid from Incarvillea sinensis

A novel monoterpene alkaloid, named incarvillateine E, possessing three moles of incarvilline moieties, has
been obtained from the aerial parts of Incarvillea sinensis LAM. (Bignoniaceae). On the basis of spectroscopic evidence,
the structure of incarvillateine E has been characterized.

 

[izo]

2000 - Two novel actinidine-type monoterpene alkaloids from Incarvillea delavayi

Two new actinidine-type monoterpene alkaloids, delavayines B (1) and C (2), were isolated from the MeOH extract of the aerial parts of Incarvillea delavayi, a close species of which, I. sinensis, is used as an analgesic for rheumatic pain in China, and the structures have been elucidated on the basis of spectroscopic evidence.

 

[izo]

2018 - Ferulic acid dimer as a non-opioid therapeutic for acute pain

Purpose: Search for alternate pain medications has gained more importance in the past few
years due to adverse effects associated with currently prescribed drugs including nervous system
dysfunction with opioids, gastrointestinal discomfort with nonsteroidal anti-inflammatory drugs,
and cardiovascular anomalies with cyclooxygenase-2 (COX-2) inhibitors. Phytomedicine has
been explored for the treatment of pain, as these have been used for generations in regional communities
and tend to lack major side effects in general. One such phytomedicine, incarvillateine
(INCA), derived from the Chinese herb Incarvillea sinensis has its primary antinociceptive action
through the adenosine receptor, a novel pain target. We hypothesized that derivatives of cinnamic
acid dimers, which are structurally similar to INCA, would show potent antinociceptive action
and that their effect would be mediated through adenosine receptor action.
Materials and methods: Dimers of cinnamic acid (INCA analogs) were synthesized
using cavitand-mediated photodimerization (CMP) method, which utilizes a macromolecule
(?-cyclodextrin) to control excited state reactivity of photoactive compounds. Acute pain
response was assessed by using formalin-induced licking behavior in hind paw of mice, and
neurologic function was monitored through locomotor activity, mechanical hyperalgesia, and
thermal sensitivity upon administration of test compound. For mechanistic studies, binding to
adenosine receptor was determined by using computer modeling.
Results: Ferulic acid dimer (FAD), which has the same chemical functionalities on the aromatic
ring as INCA, showed significant suppression of formalin-induced acute pain. Antinociceptive
effect was observed primarily in the inflammatory phase, and no apparent behavioral changes
related to the nervous system were noticeable. Inhibition of opioid receptor did not reverse
antinociceptive response, and modeling data suggest adenosine 3 receptor binding.
Conclusion: FAD (INCA analog) shows potent nonopioid antinociceptive action mediated
predominantly through A3AR – adenosine 3 receptor action. Further characterization and selection
of such INCA analogs will help us generate a new class of antinociceptives with precise
chemical modifications by using CMP methodology.

 

[izo]

2000 - Structure-Antinociceptive Activity Studies of Incarvillateine, a Monoterpene Alkaloid from Incarvillea sinensis

Abstract: Incarvillateine (1), a new monoterpene alkaloid car-
rying a characteristic cyclobutane ring, has been found to show
significant antinociceptive activity in a formalin-induced pain
model in mice. To investigate the correlation between its struc-
ture and antinociceptive activity, and especially to study
whether a cyclobutane ring is necessary or not for expression
of activity, we evaluated the antinociceptive activity of two
constructive units of incarvillateine, such as a monoterpene
unit (incarvilline, 3) and a phenylpropanoid unit (ferulic acid, 2)
in the formalin test, and compared activity of the units with
that of incarvillateine. Furthermore, in order to obtain more in-
formation about the structure-activity relationships, monoter-
pene alkaloid derivatives, such as incarvine C (5, a precursor of
incarvillateine), incarvine A (4, an ester compound comprised
of two monoterpene alkaloids and a monoterpene) and 3,3¢-de-
methoxy-4,4¢-dehydroxyincarvillateine (6, a synthetic new
compound), were examined. The antinociceptive effect of 3,3¢-
demethoxy-4,4¢-dehydroxyincarvillateine was equal to that of
incarvillateine. Meanwhile, the other compounds exhibited no
or weak activity. These results suggested that the cyclobutane
moiety of incarvillateine plays an important role in expression
of antinociceptive action.

 

[izo]

2015 - Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis, and possible involvement of the adenosine system

Incarvillea sinensis is a Bignoniaceae plant used to treat rheumatism and relieve pain in traditional
Chinese medicine. As a major component of I. sinensis, incarvillateine has shown analgesic activity
in mice formalin tests. Using a series of animal models, this study further evaluated the effects of
incarvillateine against acute, inflammatory, and neuropathic pain. Incarvillateine (10 or 20 mg/kg,
i.p.) dose-dependently attenuated acetic acid-induced writhing, but did not affect thermal threshold
in the hot plate test. In a Complete Freund’s Adjuvant model, incarvillateine inhibited both thermal
hyperalgesia and paw edema, and increased interleukin-1β levels. Additionally, incarvillateine
attenuated mechanical allodynia induced by spared nerve injury or paclitaxel, whereas normal
mechanical sensation was not affected. Incarvillateine did not affect locomotor activity and time
on the rotarod at analgesic doses, and no tolerance was observed after 7 consecutive daily doses.
Moreover, incarvillateine-induced antinociception was attenuated by theophylline, 1,3-dipropyl-
8-cyclopentylxanthine, and 3,7-dimethyl-1-propargylxanthine, but not naloxone, indicating that
the effects of incarvillateine on chronic pain were related to the adenosine system, but not opioid
system. These results indicate that incarvillateine is a novel analgesic compound that is effective
against inflammatory and neuropathic pain, and that its effects are associated with activation of the
adenosine system.

 

[Skorpio]

Looks like the truxillic acid backbone of some FABP5 inhibitors, which prolong endocannabinoid effects in the brain

 

[izo]

Looks like the truxillic acid backbone of some FABP5 inhibitors, which prolong endocannabinoid effects in the brain

ok there are indeed some effects the endocannabinoid system with these inhibitors:

2009 - Identification of intracellular carriers for the endocannabinoid anandamide.pdf
2014 - Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both by Decreasing Anandamide Levels and by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor ád (PPARád) in the Brain.pdf
2017 - Fatty-acid-binding protein inhibition produces analgesic effects through peripheral and central mechanisms.pdf

 

[izo]

and the papers of interest:

1999 - Strong Antinociceptive Effect of Incarvillateine, a Novel Monoterpene Alkaloid from Incarvillea sinensis.pdf
2000 - Structure-Antinociceptive Activity Studies of Incarvillateine, a Monoterpene Alkaloid from Incarvillea sinensis.pdf
2000 - Two novel actinidine-type monoterpene alkaloids from Incarvillea delavayi.pdf
2005 - A Monoterpene Alkaloid from Incarvillea sinensis.pdf
2005 - Pharmacological Study on the Novel Antinociceptive Agent, a Novel Monoterpene Alkaloid from Incarvillea sinensis.pdf
2005 - Quantitative Determination of Incarvillateine in Incarvillea sinensis by Solid Phase Extraction and High Performance Liquid Chromatography.pdf
2007 - A novel macrocyclic spermine alkaloid from Incarvillea sinensis.pdf
2012 - Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters - A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs.pdf
2015 - Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis, and possible involvement of the adenosine system.pdf
2016 - Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs, Discovery of Potent Analgesics for Neuropathic Pain.pdf
2018 - Ferulic acid dimer as a non-opioid therapeutic for acute pain.pdf
2019 - Natural product incarvillateine aggravates epileptic seizures by inhibiting GABAA currents.pdf

 

[izo]

ok, took some of this 100:1x extract orally and then took a little more than this nasally in 2 goes. it produces some kind of effects, not really strong but something is going on. hhc on which i am on atm is relatively stimulating but the extracts makes it rather more stimulating id say. gonna take a little bit more nasally.

 

[izo]

yes, its rather stimulating in character.

 

[Quasimoto]

@izo Nice report. I just saw this pop up on some random site I frequent, and I'm glad I didn't buy it.

 

[Smyth2]

Incarvillea sinensis is a wild plant distributed in northern China. The dried whole plant has been traditionally used to treat rheumatism and relieve pain as an ancient Chinese crude drug. To investigate its antinociceptive activity, we evaluated several fractions derived from the methanolic extract of Incarvillea sinensis in the formalin-induced pain model in mice. Incarvillateine, a novel monoterpene alkaloid, has been found to show significant antinociceptive activity. Here we report the antinociceptive activity of incarvillateine and compare its activity with that of morphine. Additionally, we suggest that its action may be related to influence on the central opioid pathways.

Nakamura, Motoyuki; Chi, Yu-Ming; Yan, Wen-Mei; Nakasugi, Yumiko; Yoshizawa, Toyokichi; Irino, Nobuto; Hashimoto, Fumio; Kinjo, Junei; Nohara, Toshihiro; Sakurada, Shinobu (1999). "Strong Antinociceptive Effect of Incarvillateine, a Novel Monoterpene Alkaloid from Incarvilleasinensis". Journal of Natural Products. 62 (9): 1293–1294. doi:10.1021/np990041c.