Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt.

Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food, and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries (China, Japan, Korea, Taiwan, Vietnam, and India), where it has been used as a valuable source of culinary and traditional medicinal uses. The leaves, seeds, and stems of P. frutescens are used for various therapeutic applications in folk medicine. In the absence of a comprehensive review regarding all aspects of perilla, this review aims to present an overview pertaining to the botanical drug, ethnobotany, phytochemistry, and biological activity. It was found that the taxonomic classification of perilla species is quite confused, and the number of species is vague. Perilla has traditionally been prescribed to treat depression-related disease, anxiety, asthma, chest stuffiness, vomiting, coughs, colds, flus, phlegm, tumors, allergies, intoxication, fever, headache, stuffy nose, constipation, abdominal pain, and indigestion, and acts as an analgesic, anti-abortive agent, and a sedative. Until now, 271 natural molecules have been identified in perilla organs including phenolic acids, flavonoids, essential oils, triterpenes, carotenoids, phytosterols, fatty acids, tocopherols, and policosanols. In addition to solvent extracts, these individual compounds (rosmarinic acid, perillaldehyde, luteolin, apigenin, tormentic acid, and isoegomaketone) have attracted researchers' interest for its pharmacological properties. Perilla showed various biological activities such as antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, and neuroprotection effects. Although the results are promising in preclinical studies (in vitro and in vivo), clinical studies are insufficient; therefore, further study needs to be done to validate its therapeutic effects and to ensure its safety and efficacy.

Genetic diversity and population structure analysis in Perilla frutescens from Northern areas of China based on simple sequence repeats.

In this study, 21 simple sequence repeat (SSR) markers were used to evaluate the genetic diversity and population structure among 77 Perilla accessions from high-latitude and middle-latitude areas of China. Ninety-five alleles were identified with an average of 4.52 alleles per locus. The average polymorphic information content (PIC) and genetic diversity values were 0.346 and 0.372, respectively. The level of genetic diversity and PIC value for cultivated accessions of Perilla frutescens var. frutescens from middle-latitude areas were higher than accessions from high-latitude areas. Based on the dendrogram of unweighted pair group method with arithmetic mean (UPGMA), all accessions were classified into four major groups with a genetic similarity of 46%. All accessions of the cultivated var. frutescens were discriminated from the cultivated P. frutescens var. crispa. Furthermore, most accessions of the cultivated var. frutescens collected in high-latitude and middle-latitude areas were distinguished depending on their geographical location. However, the geographical locations of several accessions of the cultivated var. frutescens have no relation with their positions in the UPGMA dendrogram and population structure. This result implies that the diffusion of accessions of the cultivated Perilla crop in the northern areas of China might be through multiple routes. On the population structure analysis, 77 Perilla accessions were divided into Group I, Group II, and an admixed group based on a membership probability threshold of 0.8. Finally, the findings in this study can provide useful theoretical knowledge for further study on the population structure and genetic diversity of Perilla and benefit for Perilla crop breeding and germplasm conservation.

Development of User-Friendly Method to Distinguish Subspecies of the Korean Medicinal Herb Perilla frutescens Using Multiplex-PCR.

Perilla (Perilla frutescens) is an economically and culturally important plant in East Asia. Plant breeding between cultivars has enhanced the genetic diversity of perilla overall, but means that functionally diverse subspecies are more difficult to identify and distinguish. In this study, we developed gene-based DNA markers to distinguish between the Korean herbal medicinal perilla varieties. We identified informative simple sequence repeat (SSR) regions on the promoter regions of the Myb-P1 and dihydroflavonol 4-reductase (DFR) genes, as well as a large insertion-deletion (indel) region in the limonene synthase (LS) gene, and developed markers to characterize the distinct subspecies differences (PfMyb-P1pro, PfDFRpro, and PfLS, respectively). Using the PfLS primers, a 430-bp region could be amplified from P. frutescens var. acuta, crispa, and f. viridis (known as Jasoyeop, Jureum-soyeop, and Chungsoyeop, respectively), but not from P. frutescens var. japonica (Dlggae). The PfMybpro primers resulted in PCR products of 314 or 316, 330, 322, and 315 bp from Dlggae, Jasoyeop, Jureum-soyeop, and Chungsoyeop, respectively, and the PfDFRpro primers resulted in products of 189 or 202, 187 or 189, 185 or 189, and 193bp, respectively, for the four perilla subspecies. Combining these three reactions into a single multiplex PCR approach resulted in subspecies-specific PCR band patterns for six common types of commercial perilla, distinguishing between three varieties of Dlggae (Cham-Dlggae, Ip-Dlggae, and Bora-Dlggae), as well as identifying Jasoyeop, Jureum-soyeop, and Chungsoyeop. These user-friendly markers will be valuable as a simple and efficient method for identifying the Korean medicinal herb Jasoyeop, as well as distinguishing between other functionally distinct subspecies, which may have broad applications in the Korean herbal industry.

[Perilla resources of China and essential oil chemotypes of Perilla leaves].

This study, based on the findings for Perilla resources, aimed to describe the species, distribution, importance, features, utilization and status of quantitative Perilla resources in China. This not only helps people to know well about the existing resources and researching development, but also indicates the overall distribution, selection and rational use of Perilla resource in the future. According to the output types, Perilla resources are divided into two categories: wild resources and cultivated resources; and based on its common uses, the cultivated resources are further divided into medicine resources, seed-used resources and export resources. The distribution areas of wild resources include Henan, Sichuan, Anhui, Jiangxi, Guangxi, Hunan, Jiangsu and Zhejiang. The distribution areas of medicine resources are concentrated in Hebei, Anhui, Chongqing, Guangxi and Guangdong. Seed-used resources are mainly distributed in Gansu, Heilongjiang, Jilin, Chongqing and Yunnan. Export resource areas are mainly concentrated in coastal cities, such as Zhejiang, Jiangsu, Shandong and Zhejiang. For the further study, the essential oil of leaf samples from different areas were extracted by the steam distillation method and analyzed by GC-MS. The differences in essential oil chemotypes among different Perilla leaves were compared by analyzing their chemical constituents. The main 31 constituents of all samples included: perillaketone (0.93%-96.55%), perillaldehyde (0.10%-61.24%), perillene (52.15%), caryophyllene (3.22%-26.67%), and α-farnesene (2.10%-21.54%). These samples can be classified into following five chemotypes based on the synthesis pathways: PK-type, PA-type, PL-type, PP-type and EK-type. The chemotypes of wild resources included PK-type and PA-type, with PK-type as the majority. All of the five chemotypes are included in cultivated resources, with PA-type as the majority. Seed-used resources are all PK-type, and export resources are all PA-type. The P. frutescens var. frutescens include five chemotypes, with PK-type as the majority. The PK-type leaves of P. frutescens var. acuta are green, while the PA-type leaves are reddish purple. The P. fruteseens var. crispa was mainly PA type with reddish purple leaves. The differences of the main chemotypes provide a scientific basis for distinguishing between Zisu and Baisu in previous literatures. Based on the lung toxicity of PK and the traditional use of Perilla, the testing standard of essential oil and Perilla herb shall be built, and PA type is recommended to be used in traditional Chinese medicine.

[Advances in research of volatile oil and its different chemotypes in leaves of Perilla frutescens].

The volatile oil is the main component in the leaves of Perilla frutescens. According to the main types of monoterpenoids or aromatic compounds, it can be divided into different chemotypes and the main chemotypes of Chinese producing Perilla are PA type (mainly containing Perilla aldehyde and limonene), PK type (mainly containing perillaketone) and PP type (subdivided as PP-a type, with apiole as its main component; PP-m type, with myristicin as its main component; PP-e type, with elemicin as main component; PP-as type, with asarone as main component). Based on the biosynthetic pathways analysis, we also found that the formation of the particular chemotype is usually controlled by a single gene or a few genes, and different types have different pharmacological effects. In this paper, the classification under the species P. frutescens, main chemotypes of the volatile oil, and their biogenesis and regulation, pharmacological effect and influence factors are summarized and reviewed.