Perilla ketone

The revealing of a novel double bond reductase related to perilla ketone biosynthesis in Perilla frutescens.[Pubmed:37391700]

BMC Plant Biol. 2023 Jun 30;23(1):345.

BACKGROUND: Perilla frutescens is widely used as both a medicine and a food worldwide. Its volatile oils are its active ingredients, and, based on the different volatile constituents, P. frutescens can be divided into several chemotypes, with Perilla ketone (PK) being the most common. However, the key genes involved in PK biosynthesis have not yet been identified. RESULTS: In this study, metabolite constituents and transcriptomic data were compared in leaves of different levels. The variation in PK levels was the opposite of that of isoegoma ketone and egoma ketone in leaves at different levels. Based on transcriptome data, eight candidate genes were identified and successfully expressed in a prokaryotic system. Sequence analysis revealed them to be double bond reductases (PfDBRs), which are members of the NADPH-dependent, medium-chain dehydrogenase/reductase (MDR) superfamily. They catalyze the conversion of isoegoma ketone and egoma ketone into PK in in vitro enzymatic assays. PfDBRs also showed activity on pulegone, 3-nonen-2-one, and 4-hydroxybenzalacetone. In addition, several genes and transcription factors were predicted to be associated with monoterpenoid biosynthesis, and their expression profiles were positively correlated with variations in PK abundance, suggesting their potential functions in PK biosynthesis. CONCLUSIONS: The eight candidate genes encoding a novel double bond reductase related to Perilla ketone biosynthesis were identified in P. frutescens, which carries similar sequences and molecular features as the MpPR and NtPR from Nepeta tenuifolia and Mentha piperita, respectively. These findings not only reveal the pivotal roles of PfDBR in exploring and interpreting PK biological pathway but also contribute to facilitating future studies on this DBR protein family.

Inhibition of Perilla frutescens Essential Oil on Pellicle Formation of Candida tropicalis and Pichia kluyveri and Its Effect on Volatile Compounds in Sichuan Pickles.[Pubmed:37107388]

Foods. 2023 Apr 9;12(8):1593.

Pellicle formation is the most typical characteristic of deteriorating fermented vegetable products. Perilla frutescens essential oil (PEO) is widely used as a useful natural preservative. However, few studies have addressed the antifungal activity and mechanism of PEO in pellicle formation microorganisms, and it is still unclear whether it can inhibit pellicle formation and affect its volatile compounds in Sichuan pickles. The current study showed that PEO can inhibit pellicle formation during fermentation of Sichuan pickles as it had significant antifungal activity against the pellicle formation microorganisms Candida tropicalis SH1 and Pichia kluyveri SH2. The minimum inhibitory concentration (MIC) of PEO against C. tropicalis SH1 and P. kluyveri SH2 was determined to be 0.4 muL/mL, and the minimum fungicidal concentrations (MFCs) were 1.6 muL/mL and 0.8 muL/mL, respectively. The antifungal mechanism was activated as a result of damage to the cell membrane, an increase in the cell permeability, a decrease in the mitochondrial membrane potential, and the inhibition of ATPase activity. Meanwhile, the addition of PEO to Sichuan pickles can enrich the profiles of volatile compounds during fermentation, including limonene, myrcene, 1,8-cineole, linalool, Perilla ketone, heptanal, hexanal, alpha-thujone and beta-terpineol and thus improve the overall sensory acceptability. These results indicated that PEO has the potential to be used as a novel food preservative to control pellicle formation in fermented vegetables.

Advances in the Pharmacological Activities and Effects of Perilla Ketone and Isoegomaketone.[Pubmed:36337585]

Evid Based Complement Alternat Med. 2022 Oct 28;2022:8809792.

As components of a traditional Chinese herbal medicine with many physiological activities, Perilla ketone and isoegomaketone isolated from perilla essential oil are important active components of Perilla frutescens. Recent studies have shown that these two compounds have promising antitumor, antifungal, antirheumatoid arthritis, antiobesity, anti-inflammatory, healing-promoting, and other activities and can be used to combat toxicity from immunotherapy. Therefore, the multitude of pharmacological activities and effects demonstrate the broad research potential of Perilla ketone and isoegomaketone. However, no reviews have been published related to the pharmacological activities or effects of Perilla ketone and isoegomaketone. The purpose of this review is as follows: (1) outline the recent advances made in understanding the pharmacological activities of Perilla ketone and isoegomaketone; (2) summarize their effects; and (3) discuss future research perspectives.

Comprehensive Comparison of Two Color Varieties of Perillae Folium by GC-MS-Based Metabolomic Approach.[Pubmed:36296382]

Molecules. 2022 Oct 11;27(20):6792.

Perillae Folium (PF), the leaf of Perilla frutescens (L.) Britt, is extensively used as culinary vegetable in many countries. It can be divided into two major varietal forms based on leaf color variation, including purple PF (Perilla frutescens var. arguta) and green PF (P. frutescens var. frutescens). The aroma of purple and green PF is discrepant. To figure out the divergence of chemical composition in purple and green PF, gas chromatography-tandem mass spectrometry (GC-MS) was applied to analyze compounds in purple and green PF. A total of 54 compounds were identified and relatively quantified. Multivariate statistical methods, including principal component analysis (PCA), orthogonal partial least-squares discrimination analysis (OPLS-DA) and clustering analysis (CA), were used to screen the chemical markers for discrimination of purple and green PF. Seven compounds that accumulated discrepantly in green and purple PF were characterized as chemical markers for the discrimination of the purple and green PF. Among these 7 marker compounds, limonene, shisool and perillaldehyde that from the same branch of the terpenoid biosynthetic pathway were with relatively higher contents in purple PF, while Perilla ketone, isoegomaketone, tocopheryl and squalene on other branch pathways were higher in green PF. The results of the present study are expected to provide theoretical support for the development and utilization of PF resources.

Effectiveness of a nutraceutical supplement containing highly standardized perilla and ginger extracts in patients with functional dyspepsia.[Pubmed:32283883]

Minerva Gastroenterol Dietol. 2020 Mar;66(1):35-40.

BACKGROUND: In Western countries functional dyspepsia (FD) has a prevalence of 10-20% among adults and although many drugs are currently available for use within clinical practice, FD remains an important challenge for physicians. Recently, food supplements that are ginger-based, along with other botanicals, have been proposed to be a possible natural alternative to pharmaceutical drugs to empirically counteract the symptoms of FD. METHODS: We have therefore retrospectively analyzed the efficacy and safety profiles of a nutraceutical containing, in addition to a highly standardized ginger root extract, a multi-fractionated botanical obtained from Perilla frutescens leaf containing an innovative bouquet of compounds, including hydrophilic polyphenols and the lipophilic terpenoid Perilla ketone. RESULTS: The results of our single-group study, obtained from patients with a diagnosis of FD who were treated with the perilla/ginger nutraceutical, demonstrated a good efficacy profile, with a significant reduction observed in nearly all evaluated symptoms (epigastric pain, heartburn, gastric reflux, nausea, borborygmi, early satiety, diarrhea/constipation) starting from the first week of treatment that was further improved after 2 weeks. The treatment was well tolerated with very mild side effects (flatulence, meteorism, gastric burning, difficulty in falling asleep) lasting 3-4 days, which disappeared without stopping the treatment. CONCLUSIONS: Despite all the limitations of our pragmatic study, we believe that the perilla and ginger supplement we have used can be considered a valid tool for an empirical approach to treating patients with FD, especially when a non-conventional drug treatment is preferable to the patient and considered suitable by the physician.

Preparative Separation of Three Monoterpenes from Perilla frutescens var. crispa Using Centrifugal Partition Chromatography.[Pubmed:30728839]

Int J Anal Chem. 2019 Jan 9;2019:8751345.

Three monoterpenes, namely, 9-hydroxy isoegomaketone (1), isoegomaketone (2), and Perilla ketone (3), were successfully separated from the supercritical carbon dioxide (SC-CO(2)) extract of the leaves of Perilla frutescens var. crispa (cv. Antisperill; Lamiaceae) by centrifugal partition chromatography (CPC). To obtain large quantities of these materials required for studies on their mechanism of action and in vivo effectiveness in inflammation, we used CPC because of its high loading capacity and reproducibility to purify the three compounds. Compound 1 (2.60 mg, 96.7% purity at 254 nm) was purified from 500 mg of the SC-CO(2) extract of P. frutescens var. crispa (cv. Antisperill), using a two-phase solvent system comprising n-hexane/ethyl acetate/ethanol/water (5:5:5:5 v/v) in a descending mode. As compounds 2 (56.1 mg, 97.6% purity at 254 nm) and 3 (78.6 mg, 96.1% purity at 254 nm) are highly volatile and difficult to recover from an aqueous mobile phase after purification during the drying process, they were obtained from the same amount of the processed extract in an ascending mode using the upper organic phase as the mobile phase (n-hexane/ethyl acetate/ethanol/water, 8:2:8:2 v/v). The structures of compounds 1-3 were confirmed by (1)H- and (13)C-NMR analysis. Thus, based on our findings, we recommend centrifugal partition chromatography as a powerful technique for purifying the active principal compounds 1 and 2 from the leaves of P. frutescens var. crispa.

Identification and quantification of essential oil content and composition, total polyphenols and antioxidant capacity of Perilla frutescens (L.) Britt.[Pubmed:30724256]

Food Chem. 2019 Mar 1;275:730-738.

The objective of this study was to investigate the volatile compounds of the leaves of ten perilla accessions as well as to determine total polyphenols, antioxidant capacity. Essential oil (EOs) content ranged from 0.33 to 1.75 mL/100 g d.w. in PS3 and J1 respectively. In this study sixty-five compounds were identified by GC-MS and characterized with the predominance of perillaldehyde, Perilla ketone, ss-dehydro-elsholtzia ketone, limonene, shisofuran, farnesene (Z, E, alpha), ss-caryophyllene, trans-shisool. The biogenesis and composition of EOs are probably attributed to several factors. JTD3 had a significantly higher polyphenol content as well as showed the highest antioxidant capacity, whereas a strong positive linear correlation was observed between them. PS1 and NP 606 produced the maximum biomass correspondingly, while a large glandular trichome density was recorded for J1. The results support that perilla is rich in natural compounds that could be developed as nutraceuticals and/or phytomedicine.

Chemical Eustress Elicits Tailored Responses and Enhances the Functional Quality of Novel Food Perilla frutescens.[Pubmed:30621323]

Molecules. 2019 Jan 6;24(1):185.

Consumer demand for fresh and functional horticultural products is on the rise. Perilla frutescens, L. Britt (Lamiaceae) is a potential specialty/niche crop for consumption and therapeutic uses with high contents of phenolic and volatile compounds. Plant growth, mineral composition, polyphenol profile and aroma volatile components of two perilla genotypes in response to salinity (non-salt control, 10, 20 or 30 mM NaCl) applied as chemical eustressor were assessed. Salinity suppressed growth and yield of both genotypes, although the red-pigmented genotype was less sensitive than the green-pigmented one. Mild (10 mM NaCl) and moderate (20 and 30 mM NaCl) salinity suppressed foliar potassium, magnesium, nitrate and chlorophyll a concentrations of both genotypes and increased the levels of rosmarinic acid, total polyphenols and target aroma volatile components. Green perilla showed higher yield and biomass production and higher content of protein, dry matter, calcium, magnesium, Perilla ketone and cis-jasmone, whereas red perilla exhibited higher content of potassium, chlorophyll a, rosmarinic acid, total polyphenols, perilla aldehyde and benzaldehyde. Our findings support that chemical eustressors such as mild to moderate salinity offer valuable means to manipulate phytochemical and aroma profiles.

GC-MS analysis of volatile compounds of Perilla frutescens Britton var. Japonica accessions: Morphological and seasonal variability.[Pubmed:28870340]

Asian Pac J Trop Med. 2017 Jul;10(7):643-651.

OBJECTIVE: To investigate the composition of volatile compounds in the different accessions of Perilla frutescens (P. frutescens) collected from various habitats of China and Japan. METHODS: In the present study, the essential oil from the leaves of P. frutescens cultivars from China and Japan was extracted by hydro-distillation and the chemical composition and concentration of the volatile components present in the oils were determined by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Among the volatile components, the major proportion was of Perilla ketone, which was followed by elemicin and beta-caryophyllene in the Chinese Perilla cultivars. The main component in the oil extracted from the Japanese accessions was myristicin, which was followed by Perilla ketone and beta-caryophyllene. We could distinguish seven chemotypes, namely the Perilla ketone (PK) type, Perilla ketone, myristicin (PM) type, Perilla ketone, unknown (PU) type, Perilla ketone, beta-caryophyllene, myristicine (PB) type, Perilla ketone, myristicin, unknown (PMU) type, Perilla ketone, elemicine, myristicin, beta-caryophyllene (PEMB) type, and the Perilla ketone, limonene, beta-cryophyllene, myristicin (L) type. Most of the accessions possessed higher essential oil content before the flowering time than at the flowering stage. The average plant height, leaf length, leaf width of the Chinese accessions was higher than those of the Japanese accessions. CONCLUSION: The results revealed that the harvest time and geographical origin caused polymorphisms in the essential oil composition and morphological traits in the Perilla accessions originating from China and Japan. Therefore, these chemotypes with desirable characters might be useful for industrial exploitation and for determining the harvest time.

Ligand characterization of CYP4B1 isoforms modified for high-level expression in Escherichia coli and HepG2 cells.[Pubmed:28073960]

Protein Eng Des Sel. 2017 Mar 1;30(3):205-216.

Human CYP4B1, a cytochrome P450 monooxygenase predominantly expressed in the lung, inefficiently metabolizes classical CYP4B1 substrates, such as the naturally occurring furan pro-toxin 4-ipomeanol (4-IPO). Highly active animal forms of the enzyme convert 4-IPO to reactive alkylating metabolite(s) that bind(s) to cellular macromolecules. By substitution of 13 amino acids, we restored the enzymatic activity of human CYP4B1 toward 4-IPO and this modified cDNA is potentially valuable as a suicide gene for adoptive T-cell therapies. In order to find novel pro-toxins, we tested numerous furan analogs in in vitro cell culture cytotoxicity assays by expressing the wild-type rabbit and variants of human CYP4B1 in human liver-derived HepG2 cells. To evaluate the CYP4B1 substrate specificities and furan analog catalysis, we optimized the N-terminal sequence of the CYP4B1 variants by modification/truncation and established their heterologous expression in Escherichia coli (yielding 70 and 800 nmol.l-1 of recombinant human and rabbit enzyme, respectively). Finally, spectral binding affinities and oxidative metabolism of the furan analogs by the purified recombinant CYP4B1 variants were analyzed: the naturally occurring Perilla ketone was found to be the tightest binder to CYP4B1, but also the analog that was most extensively metabolized by oxidative processes to numerous non-reactive reaction products.

Inhibition of Proinflammatory Cytokine Generation in Lung Inflammation by the Leaves of Perilla frutescens and Its Constituents.[Pubmed:24596623]

Biomol Ther (Seoul). 2014 Jan;22(1):62-7.

This study was designed to find some potential natural products and/or constituents inhibiting proinflammatory cytokine generation in lung inflammation, since cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are pivotal for provoking airway inflammation. In our preliminary screening procedure, the 70% ethanol extract of the leaves of Perilla frutescens (PFE) was found to clearly inhibit TNF-alpha production in the lung at 100 mg/kg, after intranasal lipopolysaccharide treatment of mice. Based on this result, ten constituents including phenylpropanoids (allyltetramethoxybenzene, caffeic acid, dillapiole, elemicin, myristicin, nothoapiole, rosmarinic acid methyl ester, rosmarinic acid) and monoterpenes (perilla aldehyde and Perilla ketone) were successfully isolated from the extract. Among them, elemicin and myristicin were found for the first time to concentration-dependently inhibit IL-1beta-treated IL-6 production from lung alveolar epithelial cells (A549) at concentrations of 10-100 muM. These findings suggest that the phenylpropanoids including elemicin and myristicin have the potential to be new inhibitory agents against lung inflammation and they may contribute, at least in part, to the inhibitory activity of PFE on the lung inflammatory response.

Essential oil composition and antimicrobial activity of Lobelia pyramidalis Wall.[Pubmed:29033708]

EXCLI J. 2011 Dec 6;10:274-279. eCollection 2011.

The essential oil of Lobelia pyramidalis was analyzed by GC and GC-MS. A total of 21 constituents comprising 77.88 % of the total oil were identified. Perilla ketone constituted 25.61 % of the oil followed by camphorquinone (12.16 %), dibutyl phthalate (10.66 %) and allyl nonanoate (8.47 %). The antimicrobial activity of the oil was evaluated using the disc diffusion method and the microdilution technique. The results showed that the oil exhibited moderate antimicrobial activity.

Bovine atypical interstitial pneumonia.[Pubmed:20619192]

Vet Clin North Am Food Anim Pract. 2010 Jul;26(2):395-407.

Bovine atypical interstitial pneumonia (AIP) is a multifaceted disease with several known causes or clinical presentations. Multiple causal agents and management practices have been associated with development of the condition. The sporadic incidence and development of disease in a variety of circumstances argues against a common infectious agent, although cases of AIP are often complicated with bacterial, viral, or mycoplasmal organisms. Lesions develop and progress as a basic response of the lung to injury. Metabolic activation of naturally occurring xenobiotic compounds such as 3-methyl indole, Perilla ketone, and 4-ipomeanol produce a clinical syndrome that is indistinguishable from naturally occurring AIP. Pulmonary injury is mediated by formation and activation of intermediate electrophilic compounds that covalently bind to cellular proteins and nucleic acids and ultimately cause cell death. Clara cells (nonciliated bronchiolar) and type I alveolar epithelial cells are primarily responsible for metabolism and activation of these naturally occurring xenobiotics.

Characteristic aroma-active compounds of Korean perilla (Perilla frutescens Britton) leaf.[Pubmed:20000853]

J Agric Food Chem. 2009 Dec 23;57(24):11537-42.

Aroma-active compounds from Korean perilla (Perilla frutescens Britton) leaf were extracted by solvent-assisted flavor evaporation (SAFE), liquid-liquid continuous extraction (LLCE), and hydrodistillation (HD) and analyzed by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-olfactometry (GC-O). Thirty-three volatile compounds were identified by GC-MS. 1-(3-Furyl)-4-methyl-1-pentanone (Perilla ketone) was found to be the most abundant volatile compound, followed in order by (Z)-3-hexenol and 1-octen-3-ol. Perilla ketone comprised 81% (93 ppm), 84% (120 ppm), and 95% (490 ppm) of the volatile compounds obtained from SAFE, LLCE, and HD, respectively. Thirteen aroma-active compounds were detected by GC-O. Perilla ketone, 1-(3-furyl)-4-methyl-3-penten-1-one (egoma ketone), and 1-(3-furyl)-4-methyl-2-penten-1-one (isoegoma ketone) were considered to be the characteristic aroma-active compounds of Korean perilla leaf. Perilla ketone, (Z)-3-hexenal (green), egoma ketone, and isoegoma ketone were the most intense aroma-active compounds in Korean perilla leaf. Other relatively intense odorants included (Z)-3-hexenol (green), (E)-2-hexenal (green), benzaldehyde (almond), 1-octen-3-one (metallic), 1-octen-3-ol (mushroom), phenylacetaldehyde (honeysuckle), linalool (lemon), and beta-caryophyllene (woody).