Progress on Pharmacological Effect of Terpinen-4-ol： A Review / 中国实验方剂学杂志

Terpine-4-ol is abundant in nature. As a cyclic monoterpenoid compound， terpine-4-ol is distributed in a variety of natural plants. It is the main component and the key active substance in many traditional Chinese essential oils， such as Melaleuca alba essential oil and coral ginger essential oil. Terpine-4-ol has anti-microbial， anti-tumor， insecticidal， anti-inflammatory， and other effects. It can treat cancer， as well as oral and cardiovascular diseases with great safety. In terms of antibacterial activity， terpine-4-ol can destroy bacterial cell walls， improve membrane permeability， and regulate bacterial migration， reproduction， and other related genes to inhibit bacterial activity. In terms of antifungal activity， terpine-4-ol can bind with ergosterol in fungal cell walls to cause fungal death. In terms of insecticidal activity， terpine-4-ol can inhibit Na+ and K+-ATPase activity and cause the death of the insect. In terms of anticancer activity， terpine-4-ol can regulate the expression of apoptosis-related proteins in cancer cells， so as to control the apoptosis of cancer cells. In this paper， the pharmacological activity and action mechanism of terpine-4-ol were reviewed to provide a reference for further research and utilization of terpine-4-ol.

Identification of the antidepressant fraction and its major chemical constituents of Radix Paeoniae Alba / 药学学报

The goal of this work was to investigate the antidepressant fraction from Radix Paeoniae Alba and identify its major chemical constituents. Corticosterone injured rat phaeochromocytoma (PC12) cells and behavioral despair depression models of mice were used to evaluate the antidepressant effects of Radix Paeoniae Alba (Bai-Shao) ethanol extract (BS-E) and its three fractions (BS-10E, BS-60E, BS-95E) isolated by macroporous resin column chromatography. Animal experimental procedures were approved by the Animal Ethics Committee of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: SLXD-20210618051). The results showed that BS-E, BS-10E and BS-60E had protective effects against PC12 cells injury induced by corticosterone, among which BS-60E had the strongest protective effect. BS-60E could significantly shorten the time of forced swimming and tail suspension in despair depression models of mice, and was identified as the antidepressant fraction of Radix Paeoniae Alba. The major chemical constituents in the antidepressant fraction were identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and their proposed fragmentation pathways in MS spectra were deduced. A total of 79 chemical constituents were identified from BS-60E, including 36 monoterpenes, 34 polyphenols, 6 oligosaccharides, and 3 other constituents, and monoterpenes and polyphenols may be major effective constituents of BS-60E.

Monoterpenes from an aqueous extract of the Angelica sinensis root head / 药学学报

Eleven monoterpenes including seven new chemical structures or new natural products covering two pairs of scalemic enantiomers, together with four known analogues, were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40C, together with preparative thin-layer chromatography as well as reversed phase and chiral HPLC. Their structures were determined by spectroscopic data analysis, combined with theoretic calculation of electronic circular dichroism (ECD) spectra and single crystal X-ray diffraction. The new structures or new natural products named (+)-/(-)-angelinones A and B [(+)-/(-)-1 and (+)-/(-)-2], angelinones C and D (3 and 4), and angelinol A (5), respectively, while the known analogues were 6β,9-dihydroxy-(+)-α-pinene (6), 1,1,5-trimethyl-2-hydroxymethyl-cyclohexa-2,5-dien-4-one (7), jasminol E (8), and (+)-trans-sobrerol (9). All the isolates were reported in this plant for the first time, except for the previously reported 6 from an ethanol extract of the aerial parts of A. sinensis, of which the structure was confirmed by X-ray crystallography in this study.

Monoterpene glucosides from an aqueous extract of Monochasma savatieri / 药学学报

Eleven monoterpene glucosides were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with acidic and enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, including six new compounds (1-4, 7 and 8), named monochasides A-D, G and H, respectively. Comparing the reported data of 9-hydroxylinaloyl 3-O-β-D-glucoside (5), (6Z)-9-hydroxylinaloyl 3-O-β-D-glucoside (6), and kankanoside D1 (9) with those obtained in this study, the absolute configurations of 6 and 9 were proved for the first time. Other two compounds were identified as 8-hydroxygeraniol 1-O-β-D-glucopyranoside (10) and 8-hydroxygeraniol 8-O-β-D-glucopyranoside (11), respectively.

Analgesic-like activity of perillyl acetate: In vivo and in silico studies

@# Objective: To evaluate the antinociceptive activity of perillyl acetate in mice and in silico simulations. Methods: The vehicle, perillyl acetate (100, 150 and/or 200 mg/kg, i.p.), diazepam (2 mg/kg, i.p.) or morphine (6 mg/kg, i.p.) was administered to mice, respectively. Rotarod test, acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate test, and tail-flick test were performed. Opioid receptors-involvement in perillyl acetate antinociceptive effect was also investigated. Results: Perillyl acetate did not affect the motor coordination of mice. However, it reduced the number of acetic acid-induced abdominal twitches and licking times in the formalin test. There was an increase of latency time in the tail-flick test of 30 and 60 minutes. Pretreatment with naloxone reversed the antinociceptive effect of perillyl acetate (200 mg/kg). In silico analysis demonstrated that perillyl acetate could bind to μ-opioid receptors. Conclusions: Perillyl acetate has antinociceptive effect at the spinal level in animal nociception models, without affecting the locomotor integrity and possibly through μ-opioid receptors. In silico studies have suggested that perillyl acetate can act as a μ-opioid receptor agonist.

4-Carvomenthenol, a monoterpene of essential oils, and its underlying effects on anti-inflammatory activity and immediate hypersensitivity reaction

Abstract The monoterpene 4-carvomenthenol (Carvo) is found in essential oils of plant. Here, we evaluate the Carvo oral pretreatment in acute inflammatory experimental models and in silico molecular docking. Mice pretreated with Carvo were challenged and submitted to the protocols: paw edema, peritonitis, scratching behavior and anaphylactic shock reaction. Besides, we used histamine H1 receptor, cyclooxygenases (COX-1 and COX-2) and phospholipase A2, as targets for molecular docking analysis. Carvo inhibited the carrageenan-induced paw edema and decreased the peritoneal influx of polymorphonuclear cells on carrageenan-challenged mice without interfering with the mononuclear cell influx. Moreover, Carvo diminished the histamine, PGE2 and compound 48/80 induced paw edematogenic effect. The monoterpene also diminished the mice scratching behavior and, surprisingly, avoided the animal death caused by compound 48/80 in 30 min. Through the docking analysis, Carvo showed favorable binding energy to the histamine H1 receptor. This study demonstrates that Carvo attenuated the allergic inflammatory process, decreasing edema, cell migration, activation of mast cells and the histamine release, probably due to interaction of Carvo with the histamine H1 receptor, ameliorating the itching and the anaphylactic shock reaction. Therefore, the results of this study indicate that Carvo has anti-inflammatory properties by reducing the histamine effects.

Chemical Constituents and Pharmacological Effects of Paeoniae Radix Rubra： A Review / 中国实验方剂学杂志

Paeoniae Radix Rubra is a traditional Chinese medicine commonly used in clinical practice， it is mostly wild and widely distributed in different areas of China. In addition， the plant of Paeoniae Radix Rubra also has ornamental value. Modern phytochemical researches showed that the chemical constituents of Paeoniae Radix Rubra were complex. Up to now， more than 300 chemical constituents have been found， mainly including monoterpene glycosides， triterpenoids， flavonoids， tannins， phenolic acids， saccharides， steroids， volatile oils and so on. Among them， the content of monoterpene glycosides was the highest， and the types of volatile oil were the most. Paeoniae Radix Rubra has a wide range of pharmacological effects， exerting different curative effects in multiple systems such as blood， cardiovascular， nervous and digestive system. It can protect myocardial cells and nerve cells， stabilize microcirculation， anti-endotoxin， anti-atherosclerosis， reduce pulmonary hypertension， anti-depression， protect liver， anti-gastric ulcer， anti-tumor， slow down aging， treat Parkinson's syndrome and diabetes and its complications， anti-radiation， anti-inflammatory， anti-virus and so on. Through reviewing the literature on chemical constituents and pharmacological effects of Paeoniae Radix Rubra， it was found that total glycosides and monomers such as paeoniflorin， albiflorin， benzoylpaeoniflorin and gallic acid may be the main active components of Paeoniae Radix Rubra. At present， the research on Paeoniae Radix Rubra mainly focused on monoterpene glycosides， while the research on flavonoids and volatile oil in Paeoniae Radix Rubra was less. It is suggested that research on these two components should be strengthened in the future.

Gene Cloning and Bioinformatics Analysis of Limonene-3-hydroxylase from Schizonepeta tenuifolia / 中国实验方剂学杂志

Objective:This paper aims to clone the cDNA sequence of<italic> limonene</italic>-3-<italic>hydroxylase</italic>（<italic>StL</italic>3<italic>OH</italic>） in <italic>Schizonepeta tenuifolia</italic> and analyze its sequence by bioinformatics. Method:Specific primers were designed based on sequences of<italic> StL</italic>3<italic>OH </italic>gene screened from transcriptome sequencing data of <italic>S. tenuifolia</italic> and the cDNA sequence of <italic>StL</italic>3<italic>OH </italic>gene was cloned by reverse transcription polymerase chain reaction （RT-PCR） and analyzed for its bioinformatics. Result:The <italic>StL3OH</italic> gene cDNA sequence length was 1 598 bp，containing a 1 497 bp long complete open reading frame which encoded 498 amino acids. StL3OH protein had a theoretical relative molecular mass of 56.40 kDa，with a hydrophilic and unstable nature. Bioinformatics analysis showed that StL3OH protein had no signal peptide but had a transmembrane domain which might be located in endoplasmic reticulum. Multiple sequence alignment and cluster analysis showed that the amino acid sequence of MsL3OH protein had a high similarity with StL3OH protein，both of which contained cytochrome P450 heme binding region，belonging to the D subfamily of cytochrome CYP71 family. Codon bias analysis showed that <italic>StL</italic>3<italic>OH</italic> gene preferred guanine/cytosine（G/C） ending codon，with 27 skewed codons， and Nicotiana benthamiana was proven to be the most suitable host for exogenous expression of <italic>StL</italic>3<italic>OH</italic> gene. Conclusion:The cDNA sequence of<italic> StL3OH</italic> gene was cloned from <italic>S. tenuifolia</italic> for the first time，which will provide a basis for further study on the structure and function of StL3OH protein and the regulation mechanism of <italic>StL3OH </italic>gene in the accumulation and biosynthesis of monoterpenes in<italic> S. tenuifolia</italic>.

A new monoterpene ester from Zingiberis Rhizoma Recens / 中国中药杂志

Five monoterpenoid compounds(1-5) were isolated and purified from the acetone fraction of the aqueous extract of Zingiberis Rhizoma Recens by MCI, Sephadex LH-20, silica gel, semi-preparative HPLC, and TLC. Their structures were identified with multiple spectroscopical methods including 1 D-NMR, 2 D-NMR, and MS. The five compounds were identified as(2E,6Z)-8-hydroxy-2,6-dimethylocta-2,6-dien-1-yl-(E)-3-(4-hydroxy-3-methoxyphenyl) acrylate(1),(2E,6E)-8-hydroxy-3,7-dimethylocta-2,6-die-noic acid(2),(E)-1,8-dihydroxy-3,7-dimethyl-2-octenoic acid(3), linalyl-β-D-glucopyranoside(4), and β-D-glucopyranoside-(2E)-3,7-dimethyl-2,6-octadien-1-yl(5), respectively.Compound 1 was a new monoterpene ester, and compounds 4-5 were isolated from this plant for the first time.

Chemical constituents of Artemisia argyi(II) / 中草药

Objective: To study the chemical constituents of Artemisia argyi. Methods: The chemical constituents were isolated by silica gel column chromatography and HPLC, and its structure were identified by their spectral data and physicochemical properties analysis. Result Thirty-one compounds were isolated from A. argyi with the structures identified as (E)-β-farnesene (1), β-amyrin acetate (2), cycloartenol acetate (3), lupelo acetate (4), n-triacontanol (5), docosanoic acid (6), octadecanoic acid (7), tetracosanoic acid (8), (2R,4aR,8aR)-3,4,4a,8a-tetrahydro-4a-hydroxy-2,6,7,8a-tetramethyl-2-(4,8,12-trimethyl)-chromene-5,8-dione (9), α-spinasterol (10), monopalmitin (11), 12β,20β-dihydroxyldamar-23-en-3-ketone (12), monostearin (13), monolinolenin (14), monolinolein (15), monoolein (16), 3-(3-methyl-2-butenyl)acetophenone-4-O-β-D-glucoside (17), (-)cis-chrysan-thenol-β-D-glucoside (18), artemisioside (19), (1S,2S,4R)-p-menthane-1,2,8-triol-2-O-glucoside (20), (2E,6R)-2,6-dimethyl-2,7-octadiene-6-hydroxy-1-O- glycoside (21), ampelopsisionoside (22), 4-hydroxy acetophenone-4-O-β-D-glucoside (23), skimmin (24), scopoletin (25), dendanthemoside B (26), (4R)-p-menth-1-ene-7,8-diol-7-O-β-D-glucoside (27), (4R)-p-menthane-7,8-diol-7-O-β-D-glucoside (28), isorhoifolin (29), 1,3-dicaffeoylquinic acid (30) and pinitol (31). Conclusion: Compounds 1, 9, 17, 20, 21, 26, 28 are separated from Artemisia genus for the first time. Compounds 11, 12, 14-16, 18, 19, 23, 24, 27, 30, 31 are isolated from A. argyi for the first time.

Chemical constituents from ethyl acetate soluble extraction of Litsea cubeba / 中国中药杂志

Chemical investigation on the constituents of the ethyl acetate soluble extraction of Litsea cubeba has resulted in the isolation and structure elucidation of thirty compounds, including one sesquiterpene(1), four monoterpenes(2-5), two γ-butyrolactone derivatives(6 and 7), seven tyramine derivatives(8-14), fifteen aromatic compounds(15-29), and one pyrone derivative(30) via various chromatographic techniques and spectroscopic data analysis(MS, IR, 1 D and 2 D NMR). Compounds 1-7, 13 and 14 were obtained from the genus Litsea for the first time.

Whole-genome sequencing and analysis of the Chinese herbal plant

Background@# () (2n = 2x = 16) is genus of flowering plants belonging to the Gelsemicaeae family.@*Method@#Here, a high-quality genome assembly using the Oxford Nanopore Technologies (ONT) platform and high-throughput chromosome conformation capture techniques (Hi-C) were used.@*Results@#A total of 56.11 Gb of raw GridION X5 platform ONT reads (6.23 Gb per cell) were generated. After filtering, 53.45 Gb of clean reads were obtained, giving 160 × coverage depth. The genome assemblies 335.13 Mb, close to the 338 Mb estimated by k-mer analysis, was generated with contig N50 of 10.23 Mb. The vast majority (99.2%) of the assembled sequence was anchored onto 8 pseudo-chromosomes. The genome completeness was then evaluated and 1338 of the 1440 conserved genes (92.9%) could be found in the assembly. Genome annotation revealed that 43.16% of the genome is composed of repetitive elements and 23.9% is composed of long terminal repeat elements. We predicted 26,768 protein-coding genes, of which 84.56% were functionally annotated.@*Conclusion@#The genomic sequences of could be a valuable source for comparative genomic analysis in the Gelsemicaeae family and will be useful for understanding the phylogenetic relationships of the indole alkaloid metabolism.

Simultaneous Determination of 15 Monoterpene Glycosides in Radix Paeoniae Alba and Seed Cake of Peony by HPLC / 中国药学杂志

OBJECTIVE: To establish an HPLC method for simultaneous determination of 15 monoterpene glycosides in Radix Paeoniae Alba and seed cake of peony. METHODS: The separation was performed on an Agilent Zorbax SB C18-Aq column, using acetonitrile (A) and potassium dihydrogen phosphate solution (B) (pH 2.8) as the mobile phase by gradient elution. The elution program was as follows: 0 min(A, 9%)→8 min(A, 9%)→10 min(A, 15%)→25 min(A, 20%)→42 min(A, 35%)→50 min(A, 35%). The flow rate was 1.0 mL•min-1. The detection wavelength was maintained at 260 nm. The column temperature was set at 30 ℃. RESULTS: The linear range was 5.1-81.6 μg•mL-1 for pyrindylpaeoniflorin, 12.95-207.2 μg•mL-1 for mudanpioside F, 6.2-99.2 μg•mL-1 for oxyalbiflorin, 12.2-195.2 μg•mL-1 for oxypaeoniflorin, 8.0-128.0 μg•mL-1 for 10-hydroxypaeoniflorin, 5.5-88.0 μg•mL-1 for albiflorin, 6.0-96.0 μg•mL-1 for paeoniflorin, 6.0-96.0 μg•mL-1 for oxypaeonidanin, 5.6-89.6 μg•mL-1 for 4-O-methyl-oxypaeoniflorin, 4.7-75.2 μg•mL-1 for galloylpaeoniflorin, 5.4-86.4 μg•mL-1 for 4-O-methyl-paeoniflorin, 5.0-80.0 μg•mL-1 foralbiflorin R1, 5.7-91.2 μg•mL-1 for paeonidanin, 5.4-86.4 μg•mL-1 for benzoyloxypaeoniflorin and 6.7-107.2 μg•mL-1 for benzoylpaeoniflorin. The average recoveries of the 15 monoterpene glycosides, were between 96.8%-105.6% and the RSD values were 1.05%-3.41%. CONCLUSION: The method is simple, accurate and can be used for the quality control of peony.

Cloning and characterization of a monoterpene synthase gene from Tripterygium wilfordii / 中国中药杂志

Tripterygium wilfordii is a medicinal plant commonly used in the treatment of rheumatoid arthritis,and with pharmacological activities in anti-tumor and obesity treatment. The known active ingredients in T. wilfordii are mainly terpenoids,but with very low content. Therefore,the analysis of the biosynthesis pathway of terpenoids in T. wilfordii has become a research hotspot to solve the problem of its resources. Terpenoid synthase( TPS) is a key enzyme that catalyzes the formation of a wide variety of terpenoid skeletons. In this study,a gene fragment with an ORF of 1 785 bp was cloned from T. wilfordii. Bioinformatics analysis was performed using NCBI's BLASTP,ProtParam and Interpro online tools and MEGA 6.0 software. The response of this gene to methyl jasmonate was also detected by real-time fluorescent quantitative PCR,and its catalytic function was verified by prokaryotic expression and in vitro enzymatic assay. Bioinformatics analysis indicated that the amino acid sequence encoded by this gene had both N-terminal domain and C-terminal domain of TPS,as well as the DDxx D conserved domain of the class I of TPS family. And Tw MTS gathered together with TPS-b subfamily in the Neighbor-Joining Tree constructed with known homologous TPSs. The results of RT-PCR showed that 50 μmol·L-1 MeJA 12 h could increase the expression of Tw MTS to 735 times in the control group at 12 h,and 1 644 times at 24 h. In addition,in vitro enzymatic reaction results showed that Tw MTS can catalyze the production of β-citronellol with GPP as substrate,indicating that Tw MTS was a monoterpene synthase. The above results provided a new element for the synthetic biology database of T. wilfordii terpenoids,and laid the foundation for future biosynthesis research.

Alkaloids from an aqueous extract of Uncaria rhynchophylla / 药学学报

Five alkaloids were isolated from a decoction of Uncaria rhynchophylla by a combination of various chromatographic techniques, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and reversed phase HPLC. Their structures were characterized by comprehensive analyses of spectroscopic data as monoterpene indole alkaloids (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-dihydrorhynchohylline (1), (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-dihydrorhyncho-hylline (2), (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (3) and (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (4), and a β-carboline alkaloid 1,2,3,4-tetrahydro-1-oxo-β-carboline (5). Among them, 1 and 2 are new compounds, 3 and 4 are new natural products that were semi-synthesized from isorhynchohylline with incorrect specific rotations, and 5 is isolated for the first time from the genus Uncaria.

Identification and Secondary Metabolites of Endophytic Fungus MD76 from Paeonia suffruticosa / 中国药学杂志

In order to identify the endophytic fungus MD76 and isolate its secondary metabolite. METHODS: The identification of strain MD76 is based on morphological characteristics and sequence alignment analysis of 18s rDNA ITS, the secondary metabolites were isolated by chromatography technology; and their structures were elucidated by extensive spectroscopic analysis. RESULTS: The strain MD76 was identified as Phyllosticta capitalensis; and seven compounds were gained, including benzoic acid(1), 4-hydroxybenzoic acid(2), 4-hydroxybenzene propanoic acid(3), paeoniflorin(4), oxypaeoniflorin(5), gallic acid(6), apigenin(7). CONCLUSION: The endophytic fungus P. capitalensis was gained firstly from Paeonia suffruticosa and seven compounds were isolated from P. capitalensis for the first time.

Chemical constituents from stems of Uncaria lancifolia / 中草药

Objective To study the chemical constituents from the stems of Uncaria lancifolia. Methods The isolation and purification were carried out by silica gel column chromatography, RP18, Sephadex LH-20, and preparative HPLC. The structures of the isolated compounds were elucidated by physical and chemical properties, and spectroscopic methods. Results Eighteen compounds were isolated and identified from 95% ethanol extract from the stems of U. lancifolia and characterized as uncarine A (1), uncarine E (2), isomitraphylline (3), tetrahydroalstonine (4), strictosidine (5), cadambine (6), glabratine (7), strictosamide (8), (13R)-hydroxy- octodeca-(9Z,11E,15Z)-trien-oic acid (9), (6S,9R)-roseoside (10), periplanetin (11), integracin A (12), integracin B (13), 6β,19α- dihydroxyurs-3-oxours-12-en-28-oic aicd (14), ursolic acid (15), oleanic acid (16), β-sitosterol (17), and β-daucosterol (18). Conclusion This is the first report for the chemical constituents from U. lancifolia. All compounds are obtained from this plant for the first time, and compounds 9-13 are isolated from Uncaria genus for the first time. Compounds 1-8 are monoterpene indole alkaloids, which are characteristic constituents in Uncaria genus.

Two new monoterpene glucosides from roots of Aruncus sylvester / 中草药

Objective To study the chemical constituents from the roots of Aruncus sylvester. Methods The compounds were separated and purified by D101 macroporous resin, silica gel and ODS column chromatography. Their structures were elucidated by extensive spectroscopic methods including 1D and 2D NMR, HR-ESI-MS and ECD spectrum. Results Two new monoterpene glucosides were isolated from A. sylvester, and identified as (2E,4S,5R)-4-hydroxy-3-[2-(β-D-glucopyranosyloxy)ethylidene]- 5-(2-methylprop-1-en-1-yl) dihydrofuran-2(3H)-one (1) and (2Z,4S,5R)-4-hydroxy-3-[2-(β-D-glucopyranosyloxy) ethylidene]-5- (2-methylprop-1-en-1-yl) dihydrofuran-2 (3H)-one (2). Conclusion Compounds 1 and 2 are new compounds, and named as sylvesteroside A and sylvesteroside B, respectively.

Advances in metabolic engineering for the microbial production of naturally occurring terpenes-limonene and bisabolene: a mini review / 生物工程学报

Limonene (C₁₀H₁₆) and bisabolene (C₁₅H₂₄) are both naturally occurring terpenes in plants. Depending on the number of C₅ units, limonene and bisabolene are recognized as representative monoterpenes and sesquiterpenes, respectively. Limonene and bisabolene are important pharmaceutical and nutraceutical products used in the prevention and treatment of cancer and many other diseases. In addition, they can be used as starting materials to produce a range of commercially valuable products, such as pharmaceuticals, nutraceuticals, cosmetics, and biofuels. The low abundance or yield of limonene and bisabolene in plants renders their isolation from plant sources non-economically viable. Isolation of limonene and bisabolene from plants also suffers from low efficiency and often requires harsh reaction conditions, prolonged reaction times, and expensive equipment cost. Recently, the rapid developments in metabolic engineering of microbes provide a promising alternative route for producing these plant natural products. Therefore, producing limonene and bisabolene by engineering microbial cells into microbial factories is becoming an attractive alternative approach that can overcome the bottlenecks, making it more sustainable, environmentally friendly and economically competitive. Here, we reviewed the status of metabolic engineering of microbes that produce limonene and bisabolene including microbial hosts, key enzymes, metabolic pathways and engineering of limonene/bisabolene biosynthesis. Furthermore, key challenges and future perspectives were discussed.

Perillanolides A and B, new monoterpene glycosides from the leaves of Perilla frutescens

Abstract Two new monoterpene glycosides, perillanolides A and B, together with a known compound reported from the genus Perilla for the first time were isolated and characterized from the leaves of Perilla frutescens (L.) Britton, Lamiaceae, a garnish and colorant for foods as well as commonly used for traditional medicine. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from nuclear magnetic resonance experiments, mass spectrometry and by comparing their physical and spectroscopic data of literature. These compounds, together with the previously isolated secondary metabolites of this species, were investigated for their inhibitory effects on xanthine oxidase in vitro. Of the compounds, luteolin showed the strongest inhibitory activity with an IC50 value of 2.18 µM. Esculetin and scutellarein moderately inhibited the enzyme, while perillanolides A and B, and 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside exerted weak activities.