1.Identification of Lonicera japonica TPS gene family and expression analysis under aphid damage.
Gang WANG ; Yuan CUI ; Qi-Dong LI ; Lu-Yao HUANG ; Zhen-Hua LIU ; Jia LI
China Journal of Chinese Materia Medica 2025;50(8):2116-2129
This study explores the basic characteristics and potential functions of the terpene synthase(TPS) gene family members in Lonicera japonica. The L. japonica TPS(LjTPS) gene family was identified and functionally analyzed using bioinformatics methods. The results showed that a total of 70 members of the LjTPS gene family were identified in L. japonica, with protein lengths ranging from 130 to 1 437 amino acids. Most of these proteins were hydrophilic, and they were unevenly distributed across nine chromosomes. Phylogenetic analysis showed that the LjTPS gene family members were divided into six subfamilies, mainly consisting of members from the TPS-a, TPS-b, and TPS-e subfamilies. Promoter cis-acting element analysis showed that LjTPS members contained a large number of stress-responsive cis-acting elements. Aphid inoculation experiments showed that key enzyme genes in the MVA pathway for terpenoid backbone synthesis in L. japonica, such as HMGS, HMGR, MK, MPD, and the key enzyme gene in the DXP pathway, DXS, exhibited an initial increase followed by a decrease under aphid stress. The qRT-PCR analysis showed that the expression levels of the α-farnesene synthase genes LjTPS34 and LjTPS39 were down-regulated, while the expression levels of(E)-β-caryophyllene synthase genes LjTPS15 and LjTPS17 were up-regulated 12 h before aphid feeding, then began to decline. Farnesyl pyrophosphate synthase(FPS), which interacted with these genes, also displayed a pattern of increasing followed by decreasing expression. The expression of linalool synthase genes LjTPS12 and LjTPS33 was significantly up-regulated after 72 h of aphid feeding(P<0.000 1), reaching 24.39 and 22.64 times the initial expression, respectively. This pattern was in close alignment with the trend of linalool content in L. japonica. This study provides a theoretical foundation for future research on the interaction between L. japonica and pests, as well as on the functional roles of the LjTPS gene family.
Animals
;
Aphids/physiology*
;
Alkyl and Aryl Transferases/chemistry*
;
Lonicera/parasitology*
;
Phylogeny
;
Plant Proteins/chemistry*
;
Gene Expression Regulation, Plant
;
Multigene Family
;
Terpenes/metabolism*
2.Therapeutic effects of natural products on animal models of chronic obstructive pulmonary disease.
Xinru FEI ; Guixian YANG ; Junnan LIU ; Tong LIU ; Wei GAO ; Dongkai ZHAO
Journal of Central South University(Medical Sciences) 2025;50(6):1067-1079
Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology*
;
Animals
;
Disease Models, Animal
;
Biological Products/pharmacology*
;
Humans
;
NF-kappa B/metabolism*
;
Flavonoids/pharmacology*
;
Signal Transduction/drug effects*
;
Anti-Inflammatory Agents/pharmacology*
;
Heme Oxygenase-1/metabolism*
;
Terpenes/pharmacology*
;
Antioxidants/pharmacology*
;
NF-E2-Related Factor 2/metabolism*
;
Smoke/adverse effects*
;
Phenols/therapeutic use*
3.Hypericin ameliorates stress-induced depressive-like behaviors in mice by modulating the CN-NFAT calcium signaling pathway in microglia.
Zhengtao GAO ; Pingyan LIN ; Bingcan ZHOU ; Mingheng CHEN ; Erqi LIU ; Tianxiang LEI ; Huixin NI ; Haixin LIU ; Yao LIN ; Qian XU
Journal of Southern Medical University 2025;45(3):506-513
OBJECTIVES:
To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice.
METHODS:
C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (n=15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting.
RESULTS:
Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS.
CONCLUSIONS
Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.
Animals
;
Mice, Inbred C57BL
;
Mice
;
Microglia/drug effects*
;
Depression/etiology*
;
Perylene/pharmacology*
;
Calcineurin/metabolism*
;
NFATC Transcription Factors/metabolism*
;
Calcium Signaling/drug effects*
;
Stress, Psychological
;
Phloroglucinol/pharmacology*
;
Signal Transduction
;
Male
;
Behavior, Animal/drug effects*
;
Terpenes
4.Genome-wide identification of bZIP family genes and screening of candidate AarbZIPs involved in terpenoid biosynthesis in Artemisia argyi.
Bo-Han CHENG ; Meng-Yue WANG ; Lan WU ; Ran-Ran GAO ; Qing-Gang YIN ; Yu-Hua SHI ; Li XIANG
China Journal of Chinese Materia Medica 2023;48(19):5181-5194
Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.
Gene Expression Profiling
;
Phylogeny
;
Artemisia/genetics*
;
Basic-Leucine Zipper Transcription Factors/metabolism*
;
Terpenes
;
Gene Expression Regulation, Plant
5.Identification and analysis of terpene synthase (TPS) gene family in Schizonepeta tenuifolia.
Cong-Ling JIA ; Juan SHU ; Jing-Jie DANG ; Xue WANG ; Qi-Nan WU ; Chan-Chan LIU
China Journal of Chinese Materia Medica 2023;48(22):6039-6050
Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Phylogeny
;
Terpenes/metabolism*
;
Plant Proteins/metabolism*
;
Lamiaceae/genetics*
;
Sesquiterpenes
6.RNA Methylome Reveals the m6A-mediated Regulation of Flavor Metabolites in Tea Leaves under Solar-withering.
Chen ZHU ; Shuting ZHANG ; Chengzhe ZHOU ; Caiyun TIAN ; Biying SHI ; Kai XU ; Linjie HUANG ; Yun SUN ; Yuling LIN ; Zhongxiong LAI ; Yuqiong GUO
Genomics, Proteomics & Bioinformatics 2023;21(4):769-787
The epitranscriptomic mark N6-methyladenosine (m6A), which is the predominant internal modification in RNA, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m6A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m6A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea (Camellia sinensis) leaves under solar-withering conditions. Dynamic changes in global m6A level in tea leaves were mainly controlled by two m6A erasers (CsALKBH4A and CsALKBH4B) during solar-withering treatments. Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways. Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid, catechin, and theaflavin contents by triggering alternative splicing-mediated regulation. Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m6A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.
RNA/metabolism*
;
Epigenome
;
Plant Proteins/metabolism*
;
Plant Leaves/metabolism*
;
Camellia sinensis/metabolism*
;
Flavonoids
;
Terpenes/metabolism*
;
Tea/metabolism*
;
Gene Expression Regulation, Plant
7.Identification of terpene synthase gene family members in Rhododendron and its relationship with terpenoid metabolism.
Guoxia YANG ; Baoxin JIANG ; Fan HE ; Sijia LÜ ; Dongbin LI ; Yonghong JIA ; Ping ZHU ; Xiaohong XIE ; Yueyan WU
Chinese Journal of Biotechnology 2022;38(10):3740-3756
Terpene synthase (TPS) plays important roles in the synthesis of terpenoids which are the main fragrances in Rhododendron flowers. To understand the function of TPS genes in terpenoid metabolism in relation to flower aroma formation, we identified all TPS gene family members in Rhododendron by analyzing its genome database. We then used a transcriptomic approach to analyze the differential gene expression patterns of TPS gene family members in the scented flower Rhododendron fortunei compared to the non-scented flower Rhododendron 'Nova Zembla'. The contents of terpenoid compounds in petals of the above two Rhododendron species at different developmental stages were also measured by using qRT-PCR and head space-solid phase micro-extraction combined with gas chromatography-mass spectrometry. Our results showed that a total of 47 RsTPS members, with individual lengths ranged from 591 to 2 634 bp, were identified in the Rhododendron genome. The number of exons in RsTPS gene ranged from 3 to 12, while the length of each protein encoded ranged from 196 to 877 amino acids. Members of the RsTPS family are mainly distributed in the chloroplast and cytoplasm. Phylogenetic analysis showed that RsTPS genes can be clustered into 5 subgroups. Seven gene family members can be functionally annotated as TPS gene family since they were temporally and spatially expressed as shown in the transcriptome data. Notably, TPS1, TPS10, TPS12 and TPS13 in Rhododendron fortunei were expressed highly in flower buds reached the peak in the full blossoming. Correlation analysis between gene expression levels and terpenoid content indicates that the expression levels of TPS1, TPS4, TPS9, TPS10, TPS12 and TPS13 were positively correlated with the content of terpenoids in the petals of R. fortunei at all flower developmental stages, suggesting that these six genes might be involved in the aroma formation in R. fortunei.
Rhododendron/metabolism*
;
Phylogeny
;
Terpenes/metabolism*
;
Family
;
Gene Expression Regulation, Plant
8.Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.
Ling WANG ; Jin-Hua TAO ; Yi-Fan CHEN ; Yu-Meng SHEN ; Shu JIANG
Chinese journal of integrative medicine 2022;28(11):1015-1022
OBJECTIVE:
To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics.
METHODS:
Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software.
RESULTS:
The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels.
CONCLUSIONS
The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice
;
Animals
;
Colitis, Ulcerative/drug therapy*
;
Tryptophan/adverse effects*
;
Aspartic Acid
;
Dextrans/adverse effects*
;
Drugs, Chinese Herbal/adverse effects*
;
Colitis/drug therapy*
;
Biomarkers/metabolism*
;
Amino Acids/adverse effects*
;
Glycerophospholipids/therapeutic use*
;
Sphingolipids/adverse effects*
;
Bile Acids and Salts/adverse effects*
;
Glutamates/adverse effects*
;
Alanine/adverse effects*
;
Arachidonic Acids/adverse effects*
;
Linoleic Acids/adverse effects*
;
Terpenes
9.Microbial synthesis of monoterpenoids: a review.
Fan ZHANG ; Ying WANG ; Chun LI
Chinese Journal of Biotechnology 2022;38(2):427-442
Monoterpenoids that belong to the terpenoids family are usually volatile and have strong aroma. Some monoterpenoids also have antioxidant, antibacterial and anti-inflammatory activities, which make them important raw materials for medicine, food and cosmetics industry. In recent years, the heterologous synthesis of monoterpenoids by microorganisms has attracted extensive attention. However, its large-scale application is greatly hampered by the low yield and high production cost. Nowadays, the rapid development of synthetic biology provides new approaches for enhancing the production of monoterpenoids by microorganisms. Different kinds of recombinant strains can be obtained via engineering of microbial cells to produce a variety of monoterpenoids with different properties. This paper summarized the latest strategies and progress in the application of synthetic biology to produce monoterpenoids by microorganisms, including the design and modification of biosynthetic pathway, as well as the design and optimization of high-yield monoterpenoids producing chassis cells.
Biosynthetic Pathways
;
Metabolic Engineering
;
Monoterpenes/metabolism*
;
Synthetic Biology
;
Terpenes
10.Strictosidine synthase, an indispensable enzyme involved in the biosynthesis of terpenoid indole and β-carboline alkaloids.
Chinese Journal of Natural Medicines (English Ed.) 2021;19(8):591-607
Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.
Alkaloids/biosynthesis*
;
Carbolines/metabolism*
;
Carbon-Nitrogen Lyases
;
Indoles/metabolism*
;
Terpenes/metabolism*

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