Network Pharmacology and Inflammatory Microenvironment Strategy Approach to Finding the Potential Target of Siraitia grosvenorii (Luo Han Guo) for Glioblastoma

Background: Glioblastoma (GBM) is the most common and aggressive primary intracranial tumor of the central nervous system, and the prognosis of GBM remains a challenge using the standard methods of treatment—TMZ, radiation, and surgical resection. Traditional Chinese medicine (TCM) is a helpful complementary and alternative medicine. However, there are relatively few studies on TCM for GBM.Purpose: We aimed to find the connection between TCM and anti-GBM.Study design: Network pharmacology and inflammatory microenvironment strategy were used to predict Siraitia grosvenorii (Luo Han Guo) target for treating glioblastoma.Methods: We mainly used network pharmacology and bioinformatics.Results: CCL5 was significantly highly expressed in GBM with poor prognostics. Uni-cox and randomForest were used to determine that CCL5 was especially a biomarker in GBM. CCL5 was also the target for SG and TMZ. The active ingredient of Luo Han Guo — squalene and CCL5 —showed high binding efficiency. CCL5, a chemotactic ligand, was enriched and positively correlated in eosinophils. CCL5 was also the target of Luo Han Guo, and its effective active integrate compound –— squalene — might act on CCL5.Conclusion: SG might be a new complementary therapy of the same medicine and food, working on the target CCL5 and playing an anti-GBM effect. CCL5 might affect the immune microenvironment of GBM.

Traceability of the geographical origin of Siraitia grosvenorii based on multielement contents coupled with chemometric techniques

Siraitia grosvenorii (LHG) is widely used as a medicinal and edible material around the world. The objective of this study was to develop an effective method for the authentication of the geographical origin of LHG in its main producing area Guangxi, China, which is identified as Chinese Protected Designation of Origin product, against other producing regions in China. The content of 14 elements (K, Na, Ca, P, Mg, Al, B, Ba, Cu, Fe, Mn, Ni, Zn, and Sr) of 114 LHG samples was determined by inductively coupled plasma optical emission spectrometry. Multivariate analysis was then performed to classify the geographical origin of LHG samples. The contents of multielement display an obvious trend of clustering according to the geographical origin of LHG samples based on radar plot and principal component analysis. Finally, three supervised statistical techniques, including linear discriminant analysis (LDA), k-nearest neighbours (k-NN), and support vector machine (SVM), were applied to develop classification models. Finally, 40 unknown LHG samples were used to evaluate the predictive ability of model and discrimination rate of 100%, 97.5% and 100% were obtained for LDA, k-NN, and SVM, respectively. This study indicated that it is feasible to attribute unknown LHG samples to its geographical origin based on its multielement content coupled with chemometric techniques.

Genome-scale Transcriptomic Insights Into the Gene-regulatory Network of Seed Abortion in Triploid Siraitia Grosvenorii

BackgroundSiraitia grosvenorii (Swingle) C. Jeffrey, also known as Luohanguo or monk fruit, is a famous traditional Chinese medicine ingredient with important medicinal value and broad development prospects. Diploid S. grosvenorii has too many seeds. Thus, studying the molecular mechanism of seed abortion in triploid S. grosvenorii, identifying the abortion-related genes, and regulating their expression will be a new direction to obtain seedless S. grosvenorii. Herein, we examined the submicroscopic structure of triploid S. grosvenorii seeds during abortion. ResultsBy measuring the content of endogenous hormones, we found that abscisic acid (ABA) and trans-zeatin (ZR) levels were significantly downregulated at days 15 and 20 after flowering. RNA-seq of triploid seeds at different developmental stages was performed to identify the key genes regulating abortion of triploid S. grosvenorii seeds. Multiple differentially expressed genes between adjacent stages were identified; seven genes were differentially expressed across all stages. Weight gene co-expression network analysis revealed that the enhancement of monoterpene and terpene metabolic processes might lead to seed abortion by reducing substrate flow to ABA and ZR.ConclusionsThese findings provide insights into the gene-regulatory network of seed abortion in triploid S. grosvenorii from different perspectives, thereby facilitating the innovation of the breeding technology of S. grosvenorii.

Exploration of the profile-effect relationship of Siraitia grosvenorii aqueous extracts related to their laxative effect on the basis of gray correlation analysis

Background Siraitia grosvenorii (binomial name Siraitia grosvenorii (Swingle) C. Jeffrey ex Lu et Z. Y. Zhang), also called Arhat Fruit or Monk’s Fruit, is a dried ripe fruit belonging to the Cucurbitaceae Family. S. grosvenorii has a long history of being used for constipation treatment in folk medicine. However, there are few studies where the laxative effect, related mechanisms, and active constituents of S. grosvenorii were investigated. This research explores the relationship between the common components and the laxative effect of aqueous extracts of S. grosvenorii from different habitats in China. Methods The fingerprints of S. grosvenorii aqueous extracts from different habitats were established by HPLC. The constipation mice model was used to investigate the laxative effect of S. grosvenorii aqueous extracts. The motilin (MTL) level in mice serum, and the water content of the large and small intestines in mice were determined. The profile-effect relationship of S. grosvenorii aqueous extracts was preliminarily clarified using gray correlation analysis. Results Nine common peaks were identified from the fingerprint of aqueous extracts of S. grosvenorii. The aqueous extracts obviously shortened the incubation period of defecation, and significantly increased the number of defecations, and the wet and dry weight of defecation in constipated mice. The profile-effect relationship indicated that seven common peaks were highly correlated with the effect of the incubation period of defecation, the number of defecations, and the wet and dry weight of defecation in mice. Conclusion This work provides a promising method for the fingerprint establishment, pharmacodynamic evaluation, and quality control of S. grosvenorii on the basis of its profile-effect relationship.

Chromosome-level genome assembly of Gynostemma pentaphyllum provides insights into gypenoside biosynthesis

Gynostemma pentaphyllum (Thunb.) Makino is an economically valuable medicinal plant belonging to the Cucurbitaceae family that produces the bioactive compound gypenoside. Despite several transcriptomes having been generated for G. pentaphyllum, a reference genome is still unavailable, which has limited the understanding of the gypenoside biosynthesis and regulatory mechanism. Here, we report a high-quality G. pentaphyllum genome with a total length of 582 Mb comprising 1,232 contigs and a scaffold N50 of 50.78 Mb. The G. pentaphyllum genome comprised 59.14% repetitive sequences and 25,285 protein-coding genes. Comparative genome analysis revealed that G. pentaphyllum was related to Siraitia grosvenorii, with an estimated divergence time dating to the Paleogene (∼48 million years ago). By combining transcriptome data from seven tissues, we reconstructed the gypenoside biosynthetic pathway and potential regulatory network using tissue-specific gene co-expression network analysis. Four UDP-glucuronosyltransferases (UGTs), belonging to the UGT85 subfamily and forming a gene cluster, were involved in catalyzing glycosylation in leaf-specific gypenoside biosynthesis. Furthermore, candidate biosynthetic genes and transcription factors involved in the gypenoside regulatory network were identified. The genetic information obtained in this study provides insights into gypenoside biosynthesis and lays the foundation for further exploration of the gypenoside regulatory mechanism.

Traceability of the Geographical Origin of Siraitia grosvenorii based on Multielement Contents coupled with Chemometric Techniques

Siraitia grosvenorii (LHG) is widely used as a medicinal and edible material around the world. The objective of this study was to develop an effective method for the authentication of the geographical origin of LHG in its main producing area Guangxi, China, which is identified as Chinese Protected Designation of Origin (PDO) product，against other producing regions in China. The content of 14 elements (K, Na, Ca, P, Mg, Al, B, Ba, Cu, Fe, Mn, Ni, Zn, and Sr) of 114 LHG samples was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Multivariate analysis was then performed to classify the geographical origin of LHG samples. The contents of multielement display an obvious trend of clustering according to the geographical origin of LHG samples based on radar plot and principal component analysis (PCA). Finally, three supervised statistical techniques, including linear discriminant analysis (LDA), k-nearest neighbours (k-NN), and support vector machine (SVM), were applied to develop classification models. Finally, 40 unknown LHG samples were used to evaluate the predictive ability of model and discrimination rate of 100%, 97.5% and 100% were obtained for LDA, k-NN, and SVM, respectively. This study indicated that it is feasible to attribute unknown LHG samples to its geographical origin based on its multielement content coupled with chemometric techniques.

Introduction, adaptation and characterization of monk fruit (Siraitia grosvenorii): a non-caloric new natural sweetener

Siraitia grosvenorii, an herbaceous perennial plant, native to the southern parts of China, is commonly used as a low-calorie natural sweetener. It contains cucurbitane-type triterpene glycosides known as mogrosides. The extract from monk fruit is about 300 times sweeter than sucrose. In spite of its immense importance and International demand, Siraitia grosvenorii (Swingle) is not commercially cultivated outside China since scientific information for cultivation of this species is lacking. Planting material of monk fruit plant was not available in India. Thus, the seeds of monk fruit were introduced in India from China after following International norms. Then the experiments were conducted on different aspects such as seed germination, morphological and anatomical characterization, phenology, flowering and pollination behaviors, and dynamic of mogroside-V accumulation in fruit. The hydropriming at 40 °C for 24 h was found effective to reduce the germination time and to increase the germination rate (77.33%). The multicellular uniseriate trichomes were observed in both the leaf surfaces, however, higher trichomes density was observed in the ventral surface of males compared to females. The microscopic view revealed that the ovary was trilocular (ovary consists three chambers) having two ovules in each chamber or locule. Most of the fruits were globose or oblong type with 5–7 cm in length and 4–7 cm diameter. Mogroside-V content in fruit at 80 days after pollination was 0.69% on dry weight basis. The rate of increase of mogroside-V accumulation from 50 to 70 days was very slow, whereas a sharp increase was observed from 70 to 80 days. The higher receptivity of stigma was observed with fully open flowers. The floral diagram and formula have also been developed for both male and female flowers. Our results highlighted that monk fruit can be grown in Indian conditions.