Institute of Chinese Materia Medica

Microbial production can be advantageous over the extraction of phytoterpenoids from natural plant sources, but it remains challenging to rationally and rapidly access efficient pathway variants. Previous engineering attempts mainly focused on the mevalonic acid (MVA) or methyl-d-erythritol phosphate (MEP) pathways responsible for the generation of precursors for terpenoids biosynthesis, and potential interactions between diterpenoids synthases were unexplored. Miltiradiene, the product of the stepwise conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP) catalyzed by diterpene synthases SmCPS and SmKSL, has recently been identified as the precursor to tanshionones, a group of abietane-type norditerpenoids rich in the Chinese medicinal herb Salvia miltiorrhiza . Here, we present the modular pathway engineering (MOPE) strategy and its application for rapid assembling synthetic miltiradiene pathways in the yeast Saccharomyces cerevisiae . We predicted and analyzed the molecular interactions between SmCPS and SmKSL, and engineered their active sites into close proximity for enhanced metabolic flux channeling to miltiradiene biosynthesis by constructing protein fusions. We show that the fusion of SmCPS and SmKSL, as well as the fusion of BTS1 (GGPP synthase) and ERG20 (farnesyl diphosphate synthase), led to significantly improved miltiradiene production and reduced byproduct accumulation. The MOPE strategy facilitated a comprehensive evaluation of pathway variants involving multiple genes, and, as a result, our best pathway with the diploid strain YJ2X reached miltiradiene titer of 365 mg/L in a 15-L bioreactor culture. These results suggest that terpenoids synthases and the precursor supplying enzymes should be engineered systematically to enable an efficient microbial production of phytoterpenoids.

Salvia miltiorrhiza is an important medicinal plant with great economic and medicinal value. The complete chloroplast (cp) genome sequence of Salvia miltiorrhiza, the first sequenced member of the Lamiaceae family, is reported here. The genome is 151,328 bp in length and exhibits a typical quadripartite structure of the large (LSC, 82,695 bp) and small (SSC, 17,555 bp) single-copy regions, separated by a pair of inverted repeats (IRs, 25,539 bp). It contains 114 unique genes, including 80 protein-coding genes, 30 tRNAs and four rRNAs. The genome structure, gene order, GC content and codon usage are similar to the typical angiosperm cp genomes. Four forward, three inverted and seven tandem repeats were detected in the Salvia miltiorrhiza cp genome. Simple sequence repeat (SSR) analysis among the 30 asterid cp genomes revealed that most SSRs are AT-rich, which contribute to the overall AT richness of these cp genomes. Additionally, fewer SSRs are distributed in the protein-coding sequences compared to the non-coding regions, indicating an uneven distribution of SSRs within the cp genomes. Entire cp genome comparison of Salvia miltiorrhiza and three other Lamiales cp genomes showed a high degree of sequence similarity and a relatively high divergence of intergenic spacers. Sequence divergence analysis discovered the ten most divergent and ten most conserved genes as well as their length variation, which will be helpful for phylogenetic studies in asterids. Our analysis also supports that both regional and functional constraints affect gene sequence evolution. Further, phylogenetic analysis demonstrated a sister relationship between Salvia miltiorrhiza and Sesamum indicum. The complete cp genome sequence of Salvia miltiorrhiza reported in this paper will facilitate population, phylogenetic and cp genetic engineering studies of this medicinal plant.

In this study, fluorescence spectroscopy in combination with UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy was employed to investigate the high affinity binding of palmatine to human serum albumin (HSA) under the physiological conditions. In the mechanism discussion it was proved that the fluorescence quenching of HSA by palmatine is a result of the formation of palmatine/HSA complex. Binding parameters calculating from Stern-Volmer method and Scatchard method showed that palmatine bind to HSA with the binding affinities of the order 10(4) L.mol(-1). The thermodynamic parameters studies revealed that the binding was characterized by negative enthalpy and positive entropy changes and the electrostatic interactions play a major role for palmatine-HSA association. Site marker competitive displacement experiments demonstrating that palmatine bind with high affinity to site I (subdomain IIA) of HSA. The specific binding distance r (2.91 nm) between donor (Trp-214) and acceptor (palmatine) was obtained according to fluorescence resonance energy transfer (FRET). Furthermore, the CD spectral result indicates that the secondary structure of HSA was changed in the presence of palmatine.

Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects.

BACKGROUND: Artemisia frigida Willd. is an important Mongolian traditional medicinal plant with pharmacological functions of stanch and detumescence. However, there is little sequence and genomic information available for Artemisia frigida, which makes phylogenetic identification, evolutionary studies, and genetic improvement of its value very difficult. We report the complete chloroplast genome sequence of Artemisia frigida based on 454 pyrosequencing. METHODOLOGY/PRINCIPAL FINDINGS: The complete chloroplast genome of Artemisia frigida is 151,076 bp including a large single copy (LSC) region of 82,740 bp, a small single copy (SSC) region of 18,394 bp and a pair of inverted repeats (IRs) of 24,971 bp. The genome contains 114 unique genes and 18 duplicated genes. The chloroplast genome of Artemisia frigida contains a small 3.4 kb inversion within a large 23 kb inversion in the LSC region, a unique feature in Asteraceae. The gene order in the SSC region of Artemisia frigida is inverted compared with the other 6 Asteraceae species with the chloroplast genomes sequenced. This inversion is likely caused by an intramolecular recombination event only occurred in Artemisia frigida. The existence of rich SSR loci in the Artemisia frigida chloroplast genome provides a rare opportunity to study population genetics of this Mongolian medicinal plant. Phylogenetic analysis demonstrates a sister relationship between Artemisia frigida and four other species in Asteraceae, including Ageratina adenophora, Helianthus annuus, Guizotia abyssinica and Lactuca sativa, based on 61 protein-coding sequences. Furthermore, Artemisia frigida was placed in the tribe Anthemideae in the subfamily Asteroideae (Asteraceae) based on ndhF and trnL-F sequence comparisons. CONCLUSION: The chloroplast genome sequence of Artemisia frigida was assembled and analyzed in this study, representing the first plastid genome sequenced in the Anthemideae tribe. This complete chloroplast genome sequence will be useful for molecular ecology and molecular phylogeny studies within Artemisia species and also within the Asteraceae family.

The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions (IRa and IRb), of 23,774 bp each, as well as large (LSC, 88,858 bp) and small (SSC, 18,672 bp) single-copy regions. A total of 129 genes were identified in the cp genome, 16 of which were duplicated within the IR regions. Relative to other plant cp genomes, the L. japonica cp genome had a unique rearrangement between trnI-CAU and trnN-GUU. In L. japonica cpDNA, rps19, rpl2, and rpl23 move to the LSC region, from the IR region. The ycf1 pesudogene in the IR region is lost, and only one copy locates in the SSC region. Comparative cp DNA sequence analyses of L. japonica with other cp genomes reveal that the gene order, and the gene and intron contents, are slightly different. The introns in ycf2 and rps18 genes are found for the first time. Four genes (clpP, petB, petD, and rpl16) lost introns. However, its genome structure, GC content, and codon usage were similar to those of typical angiosperm cp genomes. All preferred synonymous codons were found to use codons ending with A/T. The AT-rich sequences were less abundant in the coding regions than in the non-coding ones. A phylogenetic analysis based on 71 protein-coding genes supported the idea that L. japonica is a sister of the Araliaceae species. This study identified unique characteristics of the L. japonica cp genome that contribute to our understanding of the cpDNA evolution. It offers valuable information for the phylogenetic and specific barcoding of this medicinal plant.

The present paper is a continuation of our study on the Chinese traditional herb Artemisia annua L. [1-5], describing several additional constituents: quinghaosu IV and V (V, VII), quinghao acid (VIII) [6], chrysosplenol (VIa) [7] and a paraffinic alcohol; V, VII and VIII are compounds with unreported structures.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (M pro ), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3′,5′-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

The content of flavonoids especially baicalin and baicalein determined the medical quality of Scutellaria baicalensis which is a Chinese traditional medicinal plant. Here, we investigated the mechanism responsible for the content and composition of flavonoids in S. baicalensis under water deficit condition. The transcription levels of several genes which are involved in flavonoid biosynthesis were stimulated by water deficit. Under water deficit condition, fifteen up-regulated proteins, three down-regulated proteins and other six proteins were detected by proteomic analysis. The identified proteins include three gibberellin (GA)- or indoleacetic acid (IAA)-related proteins. Decreased endogenous GAs level and increased IAA level were observed in leaves of S. baicalensis which was treated with water deficit. Exogenous application of GA or α-naphthalene acelic acid (NAA) to plants grown under water deficit conditions led to the increase of endogenous GAs and the decrease of IAA and flavonoids, respectively. When the synthesis pathway of GA or IAA in plants was inhibited by application with the inhibitors, flavonoid levels were recovered. These results indicate that water deficit affected flavonoid accumulation might through regulating hormone metabolism in S. baicalensis Georgi.

A circular consensus sequencing (CCS) strategy involving single molecule, real-time (SMRT) DNA sequencing technology was applied to de novo assembly and single nucleotide polymorphism (SNP) detection of chloroplast genomes. Chloroplast DNA was purified from enriched chloroplasts of pooled individuals to construct a shotgun library for each species. The sequencing reactions were performed on a PacBio RS platform. CCS sub-reads were generated from polymerase reads that passed the native dumbbell-shaped DNA templates multiple times. The complete chloroplast genome sequence was generated by mapping all reads to the draft sequence constructed in a step-by-step manner. The full-chain, PCR-free approach eliminates the possible context-specific biases in library construction and sequencing reaction. The chloroplast genome was easily and completely assembled using the data generated from one SMRT Cell without requiring a reference genome. Comparisons of the three assembled Fritillaria genomes to 34.1 kb of validation Sanger sequences revealed 100% concordance, and the detected intraspecies SNPs at a minimum variant frequency of 15% were all confirmed. This simple approach with potential for parallel sequencing yields high-quality chloroplast genomes for sensitive SNP detection and comparative analyses. We recommend this approach for its powerful applicability for evolutionary genetics and genomics studies in plants based on the sequences of chloroplast genomes.

The family Aristolochiaceae, comprising about 600 species of eight genera, is a unique plant family containing aristolochic acids (AAs). The complete chloroplast genome sequences of Aristolochia debilis and Aristolochia contorta are reported here. The results show that the complete chloroplast genomes of A. debilis and A. contorta comprise circular 159,793 and 160,576 bp-long molecules, respectively and have typical quadripartite structures. The GC contents of both species were 38.3% each. A total of 131 genes were identified in each genome including 85 protein-coding genes, 37 tRNA genes, eight rRNA genes and one pseudogene (ycf1). The simple-sequence repeat sequences mainly comprise A/T mononucletide repeats. Phylogenetic analyses using maximum parsimony (MP) revealed that A. debilis and A. contorta had a close phylogenetic relationship with species of the family Piperaceae, as well as Laurales and Magnoliales. The data obtained in this study will be beneficial for further investigations on A. debilis and A. contorta from the aspect of evolution, and chloroplast genetic engineering.

A new polysaccharide (CMPB90-1) was isolated from cultured Cordyceps militaris by alkaline extraction. The chemical structure of CMPB90-1 was determined by analysis of physicochemical and spectral data. The backbone of CMPB90-1 is composed of (1→6)-linked α-d-glucopyranosyl and (1→3)-linked α-d-glucopyranosyl residues, with branching at O-6, which consists of (1→4)-linked β-d-mannopyranosyl and (1→6)-linked α-d-glucopyranosyl residues, respectively. β-d-Galactopyranosyl residues is the terminal unit. In vitro immunomodulatory assay revealed that CMPB90-1 promoted proliferation of splenic lymphocytes, enhanced cytotoxicity of NK cells and promoted lymphocyte secretion of the cytokine interleukin-2. Besides, CMPB90-1 upregulated T-cell subpopulation, strengthened phagocytosis function of macrophages and induced their M1 polarization. The mechanism of the effects might be due to the activation of TLR2, MAPK and NF-κB pathways. The results proposed that CMPB90-1 can be researched and developed as a new functional food.

The contents of total phenolics, total flavonoids, total anthocyanins, and total triterpenes of eight pear samples were determined, and the monomeric compounds were identified and quantitated using high-performance liquid chromatography. The in vitro antioxidant and in vivo anti-inflammatory activities of the different pear cultivars were compared. Arbutin and catechin were the dominant polyphenol compounds in the eight pear varieties, followed by chlorogenic acid, quercetin, and rutin. In addition, Xuehua pear and Nanguo pear had significantly higher total phenolics and flavonoids contents, while Dangshansu pear had the largest total triterpenes value (209.2 mg/100 g). Xuehua pear and Nanguo pear also were the highest in total anthocyanins. The pears with high total phenolics and total flavonoids contents had significantly higher antioxidant and anti-inflammatory abilities than those of other species. Anthocyanins were correlated to antioxidant capacity in pears, whereas total triterpenoids were strongly correlated to anti-inflammatory activity.

BACKGROUND: Traditional Chinese medicine uses various herbs for the treatment of various diseases for thousands of years and it is now time to assess the characteristics and effectiveness of these medicinal plants based on modern genetic and molecular tools. The herb Flos Lonicerae Japonicae (FLJ or Lonicera japonica Thunb.) is used as an anti-inflammatory agent but the chemical quality of FLJ and its medicinal efficacy has not been consistent. Here, we analyzed the transcriptomes and metabolic pathways to evaluate the active medicinal compounds in FLJ and hope that this approach can be used for a variety of medicinal herbs in the future. RESULTS: We assess transcriptomic differences between FLJ and L. japonica Thunb. var. chinensis (Watts) (rFLJ), which may explain the variable medicinal effects. We acquired transcriptomic data (over 100 million reads) from the two herbs, using RNA-seq method and the Illumina GAII platform. The transcriptomic profiles contain over 6,000 expressed sequence tags (ESTs) for each of the three flower development stages from FLJ, as well as comparable amount of ESTs from the rFLJ flower bud. To elucidate enzymatic divergence on biosynthetic pathways between the two varieties, we correlated genes and their expression profiles to known metabolic activities involving the relevant active compounds, including phenolic acids, flavonoids, terpenoids, and fatty acids. We also analyzed the diversification of genes that process the active compounds to distinguish orthologs and paralogs together with the pathways concerning biosynthesis of phenolic acid and its connections with other related pathways. CONCLUSIONS: Our study provides both an initial description of gene expression profiles in flowers of FLJ and its counterfeit rFLJ and the enzyme pool that can be used to evaluate FLJ quality. Detailed molecular-level analyses allow us to decipher the relationship between metabolic pathways involved in processing active medicinal compounds and gene expressions of their processing enzymes. Our evolutionary analysis revealed specific functional divergence of orthologs and paralogs, which lead to variation in gene functions that govern the profile of active compounds.

Parkinson's disease (PD) is a neurodegenerative disease, in which oxidative stress and mitochondrial dysfunction are responsible for neuronal apoptosis. Rapamycin plays a crucial role in reducing oxidative stress and protecting the mitochondria. However, its protective role in PD has not yet been fully elucidated. In this study, we report that pre-treatment with rapamycin provides behavioral improvements, protects against the loss of dopaminergic neurons, and alleviates mitochondrial ultrastructural injuries in a rat model of PD. Peroxide levels were lower and antioxidant activities were higher in PD rats pre-treated with rapamycin compared to the PD rats pre-treated with the vehicle. Furthermore, pre-treatment with rapamycin significantly elevated the expression of anti-apoptotic markers and reduced the levels of pro-apoptotic markers compared to pre-treatment with the vehicle. In conclusion, our results demonstrated that rapamycin reduced oxidative stress and alleviated mitochondrial injuries in the 6-hydroxydopamine (6-OHDA)-induced rat model of PD, which may subsequently contribute to its anti-apoptotic effects. The ability of rapamycin to exhibit neuroprotection in a rat model of PD may be related to its antioxidant capabilities.

The adulteration of herbal products is a threat to consumer safety. Here we surveyed the species composition of commercial Rhodiola products using DNA barcoding as a supervisory method. A Rhodiola dietary supplement DNA barcode database was successfully constructed using 82 voucher samples from 10 Rhodiola species. Based on the DNA barcoding standard operating procedure (SOP), we used this database to identify 100 Rhodiolae Crenulatae Radix et Rhizoma decoction piece samples that were purchased from drug stores and hospitals. The results showed that only 36 decoction piece sequences (40%) were authentic R. crenulata, which is recorded in Chinese Pharmacopeia, whereas the other samples were all adulterants and may indicate a potential safety issue. Among the adulterants, 35 sequences (38.9%) were authenticated as R. serrata, nine sequences (10%) were authenticated as R. rosea, which is documented in the United States Pharmacopeia, and the remaining samples were authenticated as other three Rhodiola species. This result indicates decoction pieces that are available in the market have complex origins and DNA barcoding is a convenient tool for market supervision.

A novel polysaccharide (FCPW80-2) with a molecular weight of 1.21 × 105 Da was first isolated from Ficus carica through hot water extraction and several chromatographic methods. The structure of FCPW80-2 was determined by chemical and instrumental analysis. The results showed that the backbone of FCPW80-2 consists of (1→5)-linked α-l-Ara, (1→3,6)-linked β-d-Man and (1→4,6)-linked β-d-Gal. The branches of FCPW80-2 consist of (1→4)-linked α-d-Glc and (1→3)-linked β-l-Rha terminated with (1→)-linked β-d-Glc. In vitro immunomodulatory activity assays revealed that FCPW80-2 could markedly promote the secretion of cytotoxic molecules (NO) and cytokines (TNF-α and IL-6) as well as the phagocytosis of RAW264.7 macrophages. Moreover, TLR2 was found to be a pattern recognition receptor (PRR) of FCPW80-2, and its related mitogen-activated protein kinases (MAPKs), including p-ERK, p-JNK and p-p38, were rapidly upregulated by FCPW80-2 in RAW264.7 macrophages. Furthermore, FCPW80-2 could not only upregulate the expression of p-p65 and p-IκB-α, but also cause the translocation of nuclear factor-kappa B (NF-κB) p65 from cytosol to nuclei in RAW264.7 macrophages. The results demonstrated that MAPK and NF-κB signalling pathways participated in FCPW80-2-induced macrophage activation and FCPW80-2 could be developed as a potential immunomodulating functional food.

The sweet rhizomes of Polygonatum cyrtonema are widely used as a tonic and functional food. A sensitive and rapid analytical method was developed for simultaneous identification and dynamic analysis of saccharides during steam processing in P. cyrtonema using HPLC–QTOF–MS/MS. Fructose, sorbitol, glucose, galactose, sucrose, and 1-kestose were identified, as well as a large number of oligosaccharides constituted of fructose units through β-(2→1) or β-(2→6). Polysaccharides and oligosaccharides were decomposed to monosaccharides during a steaming process, since the contents of glucose, galactose, and fructose were increased, while those of sucrose, 1-kestose, and polysaccharides were decreased. The high content of fructose was revealed to be the main determinant for increasing the level of sweetness after steaming. The samples of different repeated steaming times were shown to be well grouped and gradually shift along the PC1 (72.4%) axis by principal component analysis. The small-molecule saccharides, especially fructose, could be considered as markers for the steaming process of rhizomes of P. cyrtonema.

OBJECTIVE: Various extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) have been reported to be therapeutically efficacious in rheumatoid arthritis (RA) in China, but their mechanism of action remains unclear. We investigated the effect of triptolide, a diterpenoid triepoxide from TWHF, on the production of pro-matrix metalloproteinase 1 (proMMP-1; or procollagenase 1 or pro-interstitial collagenase 1), proMMP-3 (or prostromelysin 1), tissue inhibitors of metalloproteinases (TIMPs), and proinflammatory cytokines in human synovial fibroblasts and J774A.1 mouse macrophages. METHODS: Human synovial fibroblasts and mouse macrophages were cultured with interleukin-1alpha (IL-1alpha) or lipopolysaccharide (LPS) in the presence or absence of triptolide. The production of proMMPs 1 and 3, TIMPs 1 and 2, cyclooxygenase 1 (COX-1) and COX-2, prostaglandin E2 (PGE2), IL-1beta, and IL-6 was assayed by Western blot analysis and enzyme-linked immunosorbent assay. Gene expression of proMMPs 1 and 3, TIMPs 1 and 2, COX-1 and COX-2, IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNFalpha), and IL-6 was also monitored by Northern blot analysis and reverse transcriptase-polymerase chain reaction. RESULTS: Triptolide suppressed the IL-1alpha-induced production of proMMPs 1 and 3 and decreased their messenger RNA levels in human synovial fibroblasts. In contrast, the IL-1alpha-induced gene expression and production of TIMPs 1 and 2 were further augmented by triptolide in the synovial cells. Triptolide also inhibited the IL-1alpha-induced production of PGE2 by selectively suppressing the gene expression and production of COX-2, but not those of COX-1. In addition, triptolide suppressed the LPS-induced production of PGE2 in mouse macrophages. Furthermore, the gene expression of IL-1alpha, IL-1beta, TNFalpha, and IL-6, as well as the production of IL-1beta and IL-6, were inhibited by triptolide in the LPS-treated mouse macrophages. CONCLUSION: We have demonstrated for the first time that the therapeutic effects of TWHF in RA are due in part to the novel chondroprotective effect of triptolide via the direct suppression of the production of proMMPs 1 and 3 and the simultaneous up-regulation of TIMPs in IL-1-treated synovial fibroblasts. Triptolide's interference with gene expression of proinflammatory cytokines and its known inhibitory effects on PGE2 production are also probably very effective.

SAPO-11 nanosheets with partially filled micropores (N-SAPO-11) and a thickness of 10-20 nm were synthesized using polyhexamethylene biguanide hydrochloride (PHMB) as a mesoporogen and di-n-propylamine (DPA) as a microporous template. After Pt loading (0.5 wt%), the Pt/N-SAPO-11 catalyst exhibits higher selectivity for the isomers and lower selectivity for cracking products than conventional Pt/SAPO-11 catalysts in the hydroisomerization of n-dodecane.