Health benefits of Japanese pepper (Zanthoxylum piperitum)

Zanthoxylum piperitum (Rutaceae), also known as Szechuan (Sichuan) pepper, is an aromatic spiny shrub [1] commonly known as the Japanese pepper that has been used as a spice and a natural medicine in Japan [18]. The pulverized mature fruits of Japanese pepper are used as the standard spice for sprinkling on the broiled eel dish [1]. The essential oils of green and ripe fruits and dried pericarp of the Japanese pepper, are also commonly used in Japanese dishes as spices [24]. Image: Sichuan pepper by rduta under Creative Commons License (CC BY 2.0).

Other uses of Japanese pepper include the utilization of Sanshools, the major active constituent of Zanthoxylum piperitum, as food additives in East Asia. Sanshools cause irritant, tingling and sometimes paresthetic sensations on the tongue [14].

ZANTHOXYLUM PIPERITUM

Family: Rutaceae
Genus: Zanthoxylum
Common name: Japanese pepper, Sichuan pepper, Japanese pepper tree, Szechwan pepper, Japanese pricklyash.

ACTIVE CONSTITUENTS OF JAPANESE PEPPER

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Among the many different active constituents found in Zanthoxylum piperitum, we can mention at least:

1. Two serotonin derivatives, N,N-dimethylserotonin 5-O-β-glucoside (1a) and N-methylserotonin 5-O-β-glucoside (1b), isolated from the immature seeds, in a quantity reaching up to 0.29% and 0.15% respectively [5].
2. Six aliphatic acid amides [21]
3. Two flavonols, quercetin (1) and quercitrin (2), isolated from the leaves of Zanthoxylum piperitum [22].
4. Tannins were also found in the fruit peels in the form of polymeric proanthocyanidins. These ones showed also certain capacity to suppress the antibiotic resistance of Methicillin-resistant Staphylococcus aureus (MRSA)[20]
5. Oxygenated terpenes including citronellal, geraniol, and geranial are predominant for the potent odorant in the ripe fruit.
6. Geranial and citronellal, being 20% of the essential oil are responsible for the marked citrus-like note in the ripe fruit. In the dried pericarp, the terpenoids seemed to induce the flavor character of the dried pericarp, milder than that of the ripe fruit [24].

ANTI-CANCER PROPERTIES OF ACTIVE CONSTITUENTS OF JAPANESE PEPPER

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The extracts of Chinese/ Japanese peppercorns (Zanthoxyli Fructus) from the plant Zanthoxylum piperitum called "Hua Jiao"/"Sansho", block selectively the key kinase PAK1, with which peppercorn extracts could be potentially useful for the treatment of PAK1-dependent NF such as MPNST, in addition to a variety of PAK1-dependent cancers including breast cancers [19].

ANTI-INFLAMMATORY PROPERTIES OF ACTIVE CONSTITUENTS FOUND IN ZANTHOXYLUM PIPERITUM

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At least three studies performed on mouse models showed how a glycoprotein found in the leaves of Zanthoxylum piperitum DC, namely the 115 kDa and 24 kDa glycoprotein (ZPDC glycoprotein), exerted anti-inflammatory properties, something that lets scientists believe that Zanthoxylum piperitum could potentially be used as a source of natural compounds that would eventually block pro-inflammatory signal transduction pathways [7,8,9]. One of these studies suggested more specifically that the  Zanthoxylum piperitum glycoprotein is useful for prevention of inflammatory gastrointestinal diseases [9].

HEPATOPROTECTIVE PROPERTIES OF ACTIVE CONSTITUENTS FOUND IN ZANTHOXYLUM PIPERITUM

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Again, in another study carried out in mouse models to investigate the anti-oxidative and hepatoprotective effects of glycoprotein isolated from Zanthoxylum piperitum, it was demonstrated that the Zanthoxylum piperitum glycoprotein can be a potent hepatoprotective agent and a natural anti-oxidant [13].

USE OF ZANTHOXYLUM PIPERITUM AS INSECT REPELLENT

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One of the most reportedly repeated uses of Japanese pepper refers to its repellent properties. The essential oil of Zanthoxylum piperitum fruit may prove useful in the development of mosquito repellents as an effective personal protection measure against mosquito bites. Repellent testing of stored samples of Zanthoxylum piperitum fruit oil against A. aegypti demonstrated that repellent activity of those kept at -20 degrees C or 4 degrees C was present for a period of at least 3 months [15].

This use of Japanese pepper as repellent opens the doors to new environmentally friendly and biodegradable natural insecticides and repellents, particularly those from botanical sources. In a study, Zanthoxylum piperitum-derived essential oil was tested for repellency against mosquitoes.

The oil of  Zanthoxylum piperitum alone and also with 5% vanillin added repelled Aedes aegypti and was found to provide better protection against a wide range of natural mosquito populations than 25% DEET + 5% vanillin. While the product of DEET was effective in reducing bites with 99.7% protection, the protective effect of Z. piperitum oil product appeared complete (100%)!!!. it has protective effect against Aedes gardnerii, Anopheles barbirostris, Armigeres subalbatus, Culex tritaeniorhynchus, Culex gelidus, Culex vishnui group, and Mansonia uniformis [17].

ZANTHOXYLUM PIPERITUM FOR COSMETIC USE

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Last but not least, the uses of Zanthoxylum piperitum go further than the above-mentioned ones and don't limit to its medicinal and gastronomic properties, this plant has also been part of studies performed on its potential use as source of antioxidants for the preparation of cosmetics [10].

REFERENCES

[1] Wikipedia article on Zanthoxylum piperitum

[2] No reference.

[3] Plant names Porcher Michel H. et al. 1995 - 2020, Sorting Amomum Names. Multilingual Multiscript Plant Name Database   (M.M.P.N.D)  - A Work in Progress. School of Agriculture and Food Systems. Faculty of Land & Food Resources. The University of Melbourne. Australia. <http://www.plantnames.unimelb.edu.au/Sorting/Zanthoxylum.html >

[4] Enhanced repellency of binary mixtures of Zanthoxylum armatum seed oil, vanillin, and their aerosols to mosquitoes under laboratory and field conditions.
Kwon HW, Kim SI, Chang KS, Clark JM, Ahn YJ.
World Class University, Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.

[5] Isolation of N,N-dimethyl and N-methylserotonin 5-O-β-glucosides from immature Zanthoxylum piperitum seeds.
Yanase E, Ohno M, Harakawa H, Nakatsuka S.
Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.

[6] Inhibitory effect of phytoglycoprotein (115 kDa) on the expression of TNF-alpha and interleukin-1beta via inhibition of MAP kinase in primary cultured mouse thymocytes.
Park CH, Oh PS, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, Yongbong-Dong, South Korea.

[7] Inhibitory effect of ZPDC glycoprotein on the expression of inflammation-related cytokines through p38 MAP kinase and JNK in lipopolysaccharide-stimulated RAW 264.7 cells.
Lee SJ, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, 300 Yongbong-Dong, Gwangju, 500-757, South Korea

[8] Inhibitory effect of ZPDC glycoprotein on the expression of inflammation-related cytokines through p38 MAP kinase and JNK in lipopolysaccharide-stimulated RAW 264.7 cells.
Lee SJ, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, 300 Yongbong-Dong, Gwangju, 500-757, South Korea.

[9] ZPDC glycoprotein inhibits inflammation-related cytokine and protein via nuclear factor-kappa B in dextran sulfate sodium-stimulated ICR mouse.
Lee SJ, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, Kwangju 500-757, Republic of Korea.

[10] Biological screening of 100 plant extracts for cosmetic use (II): anti-oxidative activity and free radical scavenging activity.
Kim BJ, Kim JH, Kim HP, Heo MY.
College of Pharmacy, Kangwon National University, Chuncheon ,Korea.

[11] New polyunsaturated fatty acid amides isolated from the seeds of Zanthoxylum piperitum.
Jang KH, Chang YH, Kim DD, Oh KB, Oh U, Shin J.
College of Pharmacy, Seoul National University, Seoul, 110-460, Korea.

[12] Glycoprotein of Zanthoxylum piperitum DC has a hepatoprotective effect via anti-oxidative character in vivo and in vitro.
Lee SJ, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards using Biotechnology (BK 21), Chonnam National University, 300 Yongbong-Dong, Kwang-ju 500-757, South Korea.

[13] Glycoprotein of Zanthoxylum piperitum DC has a hepatoprotective effect via anti-oxidative character in vivo and in vitro.
Lee SJ, Lim KT.
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards using Biotechnology (BK 21), Chonnam National University, 300 Yongbong-Dong, Kwang-ju 500-757, South Korea.

[14] Hydroxy-alpha-sanshool activates TRPV1 and TRPA1 in sensory neurons.
Koo JY, Jang Y, Cho H, Lee CH, Jang KH, Chang YH, Shin J, Oh U.
The Sensory Research Center, Creative Research Initiatives, Seoul National University, College of Pharmacy, Gwanak, Shinlim-9 Dong Seoul, 151-742, Korea.

[15] Repellent activity of selected essential oils against Aedes aegypti.
Choochote W, Chaithong U, Kamsuk K, Jitpakdi A, Tippawangkosol P, Tuetun B, Champakaew D, Pitasawat B.
Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

[16] Human acyl-CoA: cholesterol acyltransferase inhibitory activities of aliphatic acid amides from Zanthoxylum piperitum DC.
Park YD, Lee WS, An S, Jeong TS.
National Research Laboratory of Lipid Metabolism & Atherosclerosis, KRIBB, Daejeon, Republic of Korea.

[17] Effectiveness of Zanthoxylum piperitum-derived essential oil as an alternative repellent under laboratory and field applications.
Kamsuk K, Choochote W, Chaithong U, Jitpakdi A, Tippawangkosol P, Riyong D, Pitasawat B.
Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

[18] Polyphenolic constituent structures of Zanthoxylum piperitum fruit and the antibacterial effects of its polymeric procyanidin on methicillin-resistant Staphylococcus aureus.
Kusuda M, Inada K, Ogawa TO, Yoshida T, Shiota S, Tsuchiya T, Hatano T.
Department of Pharmacognosy, Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama.

[19] Sichuan pepper extracts block the PAK1/cyclin D1 pathway and the growth of NF1-deficient cancer xenograft in mice.
Hirokawa Y, Nheu T, Grimm K, Mautner V, Maeda S, Yoshida M, Komiyama K, Maruta H.
Ludwig Institute for Cancer Research, Parkville/Melbourne, Australia.

[20] Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus.
Hatano T, Kusuda M, Inada K, Ogawa TO, Shiota S, Tsuchiya T, Yoshida T.
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.

[21] Aliphatic acid amides of the fruits of Zanthoxylum piperitum.
Hatano T, Inada K, Ogawa TO, Ito H, Yoshida T.
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.

[22] Tyrosinase inhibitor isolated from the leaves of Zanthoxylum piperitum.
Jeong CH, Shim KH.
Division of Applied Life Science, Graduate School and Institute of Agricultural Life Sciences, Gyeongsang National University, JinJu, Korea.

[23] Zanthoxylum piperitum (DC), a potential feeding deterrent for mammals: studies with Microtus ochrogaster (Wagner).
Epple G, Bryant BP, Mezine I, Lewis S.
Monell Chemical Senses Center, 3500 Market St, Philadelphia, PA 19104, USA

[24] Differences in the volatile components and their odor characteristics of green and ripe fruits and dried pericarp of Japanese pepper (Xanthoxylum piperitum DC.).
Jiang L, Kubota K.
Laboratory of Food Chemistry, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.

[25] Effect of methanol extract of Zanthoxylum piperitum leaves and of its compound, protocatechuic acid, on hepatic drug metabolizing enzymes and lipid peroxidation in rats.
Hur JM, Park JG, Yang KH, Park JC, Park JR, Chun SS, Choi JS, Choi JW.
Department of Oriental Medicine Resources and Research Institute of Korean Oriental Medicine, Suncheon, Jeonnam 540-742, Korea.

[26] Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated gastrointestinal tract.
Hashimoto K, Satoh K, Kase Y, Ishige A, Kubo M, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K, Nakamura T.