Japanese catnip

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

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

• 0.5-1.8% volatile oils,^[1] mostly R-(+)-Pulegone^[2][4] and Menthone^[5] with some D-Limonene, Menthofuran^[1][5] and Menthol at 0.0234%^[6]
• Monoterpenes including Schizonepetosides A-E, Schizonol, and Schizonodiol^[1][7][8]
• 2α,3α,24-trihydroxyolean-12en-28oic acid^[2]
• Ursolic Acid^[2]
• Rosmarinic Acid^[2]
• Diosmetin at 4.3+/-0.3mg/g dried leaves^[3]
• Hesperidin^[2] at 12.0+/-0.4mg/g dried leaves^[3]
• Luteolin-7-O-glucuroninide^[2] with Luteolin (aglycone) at 5.5+/-0.3mg/g dried leaves^[3]
• β-Sitosterol^[2][9]

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]

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 C_max 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 C_max by 34% and overall AUC by 29.3%) and also inhibited CYP2E1 as assessed by chlorzoxazone kinetics (76% increase in C_max and 36.1% increase in AUC).^[10] CYP2D6 was also noted to be inhibited with a 51% and 147% increase in the C_max 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

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)

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

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

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

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

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

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

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