Schizonepeta tenuifolia

Schizonepeta tenuifolia (Japanese Catnip) is a medicinal herb from China and Korea that appears to be selectively anti-inflammatory (to a moderate degree), and suppress allergic responses. It is a different herb from Common Catnip (The genera Nepeta).

This page features 22 unique references to scientific papers.

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Summary

All Essential Benefits/Effects/Facts & Information

Schizonepeta Tenuifolia is a herb that is commonly called Japanese Catnip of Jing Jie and is a traditional asian remedy (Chinese, Korean, and Japanese) for the common cold, headcolds, and allergic skin eruptions.

It has a fair bit of animal and in vitro evidence investigating possible roles in the immune system, and although it appears to be anti-inflammatory overall (a moderate level and anti-inflammation, with one study finding it comparable to Indomethacin and two studie concluding it less effective than Dexamethasone) it appears to have some selective anti-inflammatory effects. It is for these reasons Japanese Catnip is known as an immunomodulator, but currently more evidence would be needed (with some human interventions) to ascertain its role as an immune system modulator.

It currently does not have any other scientifically supported uses.

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How to Take

Recommended dosage, active amounts, other details

Traditional usage of Japanese Catnip, for fighting colds and reducing skin eruptions, was 3-10g of a decoction. There are no human studies to confirm if this is the optimal dosage range, and the animal studies (200-500mg/kg in rats) suggest dosage ranges of:

  • 2,200-5,400mg for a 150lb person

  • 2,900-7,200mg for a 200lb person

  • 3,600-9,000mg for a 250lb person

Which are the estimated human dosages for inflammation. They appear to parallel traditional recommendations somewhat.

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1Sources and Composition

1.1. Sources

Schizonepeta (of the family Labiatae) is a genera of plants known as Japanese Catnip, of which tenuifolia is a particular medicinal species given the common name Jing Jie (China) and is used in Traditional Chinese Medicine (although Schizonepeta Multifida is sometimes also referred to as Jing Jie[1]), and known as Hyung-gae in Korea. This is different from 'True' Catnip, which is the genus Nepeta of the same plant family.

Japanese Catnip appears to be used to relieve body aches, as a hemostatic, antibiotic, anti-inflammatory drug, antipyretic, and antioxidant, as well as to treat the common cold, sore throat, allergic dermatitis, eczema, and psoriasis.[2] It is sometimes presribed alongside Ledebouriella seseloides for both the common cold and skin rashes.[1]

The dried above-ground parts of S. tenuifolia is often consumed in the East in sauce, beverage, beneficial tea or herbal medicine, with various quantities being added.[3] A 'carbonized' form is also sometimes used, particularly for bloody stool and metrorrhagia, is stirfried at a high temperature untilits exterior surface becomes blackish-brown and its interior surface turns dark yellow.[1]

Leaf or leaf/stem (aerial parts) extracts have traditionally been dried and then used to fight off infections or allergies

1.2. Composition

The dry weight of the aerial (above ground) parts include:

The effects of Japanese Catnip are most likely related to either the volatile oils of the monoterpenoids, but no evidence exists to suggest what bioactive(s) is/are the main ones; all studies currently just use water extracts of the aerial parts of the plant itself

Total phenolics may reach 172mg/g (1.7%) dry leaf extract.[3]


2Pharmacology

2.1. Phase I Enzyme Interactions

Schizonepetin at an oral dose of 24mg/kg for seven days in rats appears to induce the activity of the CYP3A1/2 enzyme (assessed by dapsone pharmacokinetics, decreasing Cmax by 37% and increasing clearance by 63%); 24-48mg/kg, but not 12mg/kg, appears to induce the mRNA of this CYP isoform.[10]

The same dose of schizonepetin appears to inhibit the CYP1A2 enzyme as assessed by phenacetin kinetics (increasing Cmax by 34% and overall AUC by 29.3%) and also inhibited CYP2E1 as assessed by chlorzoxazone kinetics (76% increase in Cmax and 36.1% increase in AUC).[10] CYP2D6 was also noted to be inhibited with a 51% and 147% increase in the Cmax and AUC of metoprolol, and the former two enzymes (CYP1A2 and CYP2E1) also noted an increase in mRNA levels at 24mg/kg or higher, but not 12mg/kg.[10]

CYP2C19 appears to be unaffected by schizonepetin at the oral dose of 24mg/kg.[10]

An oral dose of 24mg/kg schizonepetin in rats (estimated human equivalent of 3.84mg/kg) but not half the dose appears to be able to influence Phase I enzymes and possible alter drug pharmacokinetics


3Inflammation and Immunology

3.1. Mechanisms

In isolated macrophages, Japanese Catnip appears to suppress TNF-α content at 50-200mcg/mL at 6 hours, with only the highest dose lasting to 24 hours; the inhibitory effect on IL-6 content was more insensitive, only occurring at the highest concentration at the 6 hour point.[11] TNF-α mRNA, but not IL-6, was suppressed with Japanese Catnip and thought to be related to inhibiting JNK/SAPK dependent c-Jun/ATF-2 activity; a member of the AP-1 family that is tied into TNF-α secretion.[4] MAPK inhibition has also been noted in macrophages, extending to all three subsets (p38, ERK, and JNK; upstream of AP-1).[12]

In activated macrophages, Japanese Catnip extract appears to be anti-inflammatory. It is not as potent as reference drugs (Dexamethasone), but appears to suppress TNF-α more than IL-6 and may be selective (Dexamethasone, and many antiinflammatories, are universally antiinflammatory)

3.2. Splenocytes

At least one study assessing cell viability noted that 100mcg/mL of the water extract was not cytotoxic, but noted mitogenic activity to a level of 1.5-2.5 that of control cells.[13]

May help proliferate immune cells, needs more resarch on the topic

3.3. T-Cells

In response to injected anti-CD3, the serum increase in IFN-γ and IL-4 mRNA expression is attenuated with prior administration of Japanese Catnip and differentation into Th1 and Th2 T-cells is attenuated.[14] A later study noted that Japanese Catnip at an oral dose of 100-500mg/kg of the water extract, after anti-CD3 injection, that the decrease in IFN-γ and IL-4 occurs to a degree larger than the mRNA reductions and serum IL-2 is increased.[14][13] IFN-γ and IL-4 are cytokines normally increased in T-Cells in response to an antigen, with STAT4 and STAT6 being increased at a later point to sustain the elevation.[15]

The currently thought mechanism of action was noted in vitro, where Japanese Catnip could suppress NF-kB translocation while simultaneously promoting (NFAT)c2 translocation.[13] An increase in phosphorylation of both STAT4 and STAT6 is noted with Japanese Catnip, but is thought to not be causative of the above cytokine changes.

Appears to possess anti-inflammatory effects in regards to T-cell differentiation, yet has some 'selective' effects where IL-2 is increased (Dexamethasone and many anti-inflammatories do not tend to influence IL-2 much) and can activate STAT4/6

3.4. Allergic Reactions

In human leukemic mast cells (HMC-1) using isolated compounds found in Japanese Catnip, 100mcg/mL of Ursolic Acid, Rosmarinic Acid, Pulegone, and 2α,3α,24-trihydroxyolean-12en-28oic acid were all able to significantly reduce Mast cell degranulation induced by either PMA or calcium ionophore (although this concentration of Ursolic acid was cytotoxic).[2] When measuring the release of IL-6, IL-8, and TNF-α, it appeared that ursolic acid was most effective of the isolated ingredients yet the Japanese Catnip per se outperfomed all isolated components at 1mcg/mL (whereas it performed equally at 100mcg/mL.[2] This seemingly anti-allergic activity has been confirmed in vivo in mice fed Japanese Catnip prior to DNCB application[16] and has been noted to reduce mortality rates induced by compound 48/80 when 0.005-1g/kg is ingested and concurrently reduced histamine concentrations.[17]

Appears to have anti-allergic effects by preventing mast cell degranulation, which have been confirmed in rodent models

3.5. Interventions

50-1000mg/kg water extract of Japanese Catnip for 10 days prior to LPS injections (proinflammatory stimuli) noted that only 200-500mg/kg (not the highest tested doses) were able to suppress TNF-α induction by approximately half, with no significant effect on IL-6;[11] Dexamethasone as drug control significantly outperformed Japanese Catnip on reducing both cytokines (91% and 50%).[11]

In a carrageenan-induced paw edema test, the reduction in antioxidative enzymes seen in control are attenuated at 500mg/kg to a similar degree as 10mg/kg Indomethacin (125-250mg/kg showing antioxidative effects, but to a lesser degree) and reduced both TNF-α, nitrate, and lipid peroxidation to similar degrees; Japanese Catnip at 500mg/kg appeared to be equally effective in reducing paw edema (indicative of inflammation associated with TNF-α and oxidation[18]) as 10mg/kg Indomethacin.[3]

The anti-inflammatory effects are preliminary, with two animal studies being conducted; that being said, it appears to be moderately potent with 500mg/kg in rats being not significantly different than 10mg/kg Indomethacin, but weaker than Dexamethasone


4Interactions with Oxidation

4.1. Mechanisms

In vitro, the dried aerial parts of Japanese Catnip show concentration-dependent antioxidative in assays on liposome protection, ABTS, and DPPH[3] with 0.2mg/mL of the water extract inhibiting up to 93.8+/-2.3% (ABTS) and 95.5+/-1.8% (DPPH) oxidation but only 31.1+/-3.8% Liposome protection.[3]

Anti-oxidative effects have been noted in vivo, with 500mg/kg of the water extract of aerial parts being as effective as 10mg/kg Indomethacin in response to carrageenan injections.[3]

Possesses anti-oxidative effects, practical relevance unknown


5Interactions with Organ Systems

5.1. Liver

The two monoterpenes, Menthofuran and Pulegone, may metabolize into a compound known as p-cresol which has been shown to cause glutathione depletion in hepatocytes,[19][20] although the volatile oil β-Myrcene appears to be hepatoprotective.[21] No studies have assessed the entire volatile oil essence of Japanese Catnip per se, so it is unknown what the overall effect is.

Volatile oils in Japanese Catnip possess both hepatotoxic and hepatoprotective properties, with the practical significance of supplemental Japanese Catnip unknown


6Interactions with Aesthetics

6.1. Skin

Anti-inflammatory properties of Japanese Catnip appears to exert protective effects against atopic dermatitis (as assessed by a mouse study inducing dematitis with DNCB).[16]

Related to the anti-allergic mechanisms of action, Japanese Catnip may suppress skin eruptions in response to inflammation or allergins


7Safety and Toxicology

The LD50 of the fat-soluble extract of Schizonepeta tenuifolia (carbonized) appears to be 2.652+/-0.286g/kg (oral) and 1.945+/-0.207g/kg (injections) in mice and rabbits.[1][22]

Scientific Support & Reference Citations

References

  1. Fung D, Lau CB Schizonepeta tenuifolia: chemistry, pharmacology, and clinical applications . J Clin Pharmacol. (2002)
  2. Sohn SH, et al Microarray analysis of the gene expression profile of HMC-1 mast cells following Schizonepeta tenuifolia Briquet treatment . Cell Immunol. (2012)
  3. Wang BS, et al Antioxidant and anti-inflammatory activities of aqueous extracts of Schizonepeta tenuifolia Briq . Food Chem Toxicol. (2012)
  4. Swantek JL, Cobb MH, Geppert TD Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK . Mol Cell Biol. (1997)
  5. Yu S, et al Quantitative Comparative Analysis of the Bio-Active and Toxic Constituents of Leaves and Spikes of Schizonepeta tenuifolia at Different Harvesting Times . Int J Mol Sci. (2011)
  6. Lin R, et al Analysis of menthol in three traditional Chinese medicinal herbs and their compound formulation by GC-MS . Biomed Chromatogr. (2002)
  7. Oshima Y, Takata S, Hikino H Schizonodiol, Schizonol, and Schizonepetosides D and E, Monoterpenoids of Schizonepeta tenuifolia Spikes1 . Planta Med. (1989)
  8. The Constituents of Schizonepeta tenuifolia BRIQ. I. Structures of Two New Monoterpene Glucosides, Schizonepetosides A and B
  9. Hwang SL, et al Beneficial effects of beta-sitosterol on glucose and lipid metabolism in L6 myotube cells are mediated by AMP-activated protein kinase . Biochem Biophys Res Commun. (2008)
  10. Bao B, et al Effects of schizonepetin on activity and mRNA expression of cytochrome p450 enzymes in rats . Int J Mol Sci. (2012)
  11. Kang H, et al Suppression of tumour necrosis factor-alpha by Schizonepeta tenuifolia water extract via inhibition of IkappaBalpha degradation and Jun N-terminal kinase/stress-activated protein kinase activation . J Pharm Pharmacol. (2010)
  12. Kim SJ, et al Anti-inflammatory activity of Schizonepeta tenuifolia through the inhibition of MAPK phosphorylation in mouse peritoneal macrophages . Am J Chin Med. (2008)
  13. Kang H, Moon JY, Sohn NW Regulation of interferon-gamma, interleukin-4 and interleukin-2 by Schizonepeta tenuifolia through differential effects on nuclear factor-kappaB, NFATc2 and STAT4/6 . Exp Biol Med (Maywood). (2010)
  14. Kang H, et al Immunomodulatory effect of Schizonepeta tenuifolia water extract on mouse Th1/Th2 cytokine production in-vivo and in-vitro . J Pharm Pharmacol. (2008)
  15. Grogan JL, et al Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets . Immunity. (2001)
  16. Choi YY, et al Schizonepeta tenuifolia Inhibits the Development of Atopic Dermatitis in Mice . Phytother Res. (2012)
  17. Shin TY, et al Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats . Immunopharmacol Immunotoxicol. (1999)
  18. Rocha AC, et al Relevance of tumour necrosis factor-alpha for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw . Br J Pharmacol. (2006)
  19. Zhou SF, et al Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update . Curr Drug Metab. (2007)
  20. Khojasteh SC, Oishi S, Nelson SD Metabolism and toxicity of menthofuran in rat liver slices and in rats . Chem Res Toxicol. (2010)
  21. Amin KA, Nagy MA Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats . Diabetol Metab Syndr. (2009)
  22. Ding NW, et al Research on hemostatic constituents in carbonized Schizonepeta tenuifolia Brig . Zhongguo Zhong Yao Za Zhi. (1993)