Plant-Derived Exosome-like Nanoparticles for Biomedical Applications and Regenerative Therapy.

Plant-derived exosome-like nanoparticles (PDENs) comprise various bioactive biomolecules. As an alternative cell-free therapeutic approach, they have the potential to deliver nano-bioactive compounds to the human body, and thus lead to various anti-inflammatory, antioxidant, and anti-tumor benefits. Moreover, it is known that Indonesia is one of the herbal centers of the world, with an abundance of unexplored sources of PDENs. This encouraged further research in biomedical science to develop natural richness in plants as a source for human welfare. This study aims to verify the potential of PDENs for biomedical purposes, especially for regenerative therapy applications, by collecting and analyzing data from the latest relevant research and developments.

Drug candidates and potential targets of Curculigo spp. compounds for treating diabetes mellitus based on network pharmacology, molecular docking and molecular dynamics simulation.

Curculigo spp. is a herb that is commonly used in Indonesia to treat diabetes mellitus (DM) . The main active components of Curculigo spp. were identified through our previous metabolomic study and online database platform. However, the biological mechanisms underlying Curculigo spp. activity in treating DM remain unclear. Therefore, in this study, a network pharmacology was used to explore the active compounds of Curculigo spp. and their potential molecular mechanisms for treating DM. Oral bioavailability and drug-likeness from the compounds of Curculigo spp. were screened using Lipinski's rule of five, BBB, HIA + and Caco-2 permeability criteria. A network of compound-target-disease-pathway was then constructed using Cytoscape. The highest degree compounds and targets were then confirmed by molecular docking and molecular dynamics (MD) simulations. The human body can absorb 33 compounds derived from Curculigo spp. In addition, 58 nodes and 62 edges generated a network analysis with the DM target. The highest degree of the compound-target-disease pathway was for orcinol glucoside, AKR1B1, autoimmune diabetes, bile acid and bile salt metabolism. Furthermore, the computational docking method on Curculigo spp. compounds with the highest degree revealed that orcinol glucoside interacted with PTPN1 through a hydrogen bond and resulted in a binding energy of -7.2 kcal mol-1. Through hydrogen bonds, orcinol glucoside in PTPN1 regulates multiple signaling pathways via the adherens junction pathway, which may play a therapeutic role in DM (type 2 diabetes: obesity). In addition, MD simulation confirmed that orcinol glucoside, is suitable for DM treatment by interacting with PTPN1.Communicated by Ramaswamy H. Sarma.

Effect of Medium pH and Light on Quinidine Production in Cinchona calisaya Wedd. Endophytic Fungi

Objectives: Quinidine has pharmaceutical importance as an antimalarial, antiarrhythmia, antimicrobial, anticancer, antioxidant, astringent, and bitter flavoring agent. Quinidine is in high demand, yet its production from the bark of the quina tree (Cinchona calisaya) is limited. Quinidine production from quina tree fungal endophytes, namely Aspergillus sydowii, Diaporthe sp., Diaporthe lithicola, Fusarium oxysporum, and F. solani is lower than the quinidine content of the tree bark. This study attempted to increase quinidine production from these fungi. This research aimed to determine the optimum culture conditions for quinidine production from endophytic fungi. Materials and Methods: Quinidine was produced by in vitro culturing of the fungal endophytes in potato dextrose broth (PDB) medium under different culture conditions, i.e., a combination of an initial medium pH of 6.2 or 6.8, with or without light, in a static condition for 21 days of incubation at room temperature. Production under natural daylight in PDB medium without pH modification was used as the control. At the end of the incubation period, the mycelial mass was separated from the filtrate. The dried biomass and chloroform-extracted filtrate were weighed. Quinidine in the extract was analyzed qualitatively and quantitatively using high-performance liquid chromatograph. Results: Quinidine production was affected by both light and the initial pH of the medium, depending on the fungal strain used. A significant increment in quinidine production, approximately 1.1-9.3-fold relative to its respective control was obtained from all fungi under their optimum conditions. Quinidine production in most of the fungi was significantly correlated with their biomass production but not with their extract production. Of those five fungi, F. solani that was cultured in PDB medium with an initial pH of 6.2 and incubated under continuous light produced the highest concentration of quinidine with low biomass. Conclusion: The quinidine production of all fungal endophytes studied was affected by the culture conditions. F. solani is the most promising fungus for use as a quinidine production agent.

Untargeted Metabolomics Analysis Using FTIR and UHPLC-Q-Orbitrap HRMS of Two Curculigo Species and Evaluation of their Antioxidant and α-Glucosidase Inhibitory Activities.

Curculigo orchioides and C. latifolia have been used as traditional medicines such as antidiabetic and anticancer. This study measured the total phenolics and flavonoid contents as well as analyzed the functional groups and chemical compounds using Fourier-transform infrared (FTIR) spectra and UHPLC-Q-Orbitrap-HRMS profiling for the discrimination of plant parts, geographical origin, and compounds that presumably have a significant contribution as antioxidant and α-glucosidase inhibitors on both plants. The total phenolics and flavonoids contents in Curculigo species varied from 142.09 to 452.47 mg gallic acid equivalent (GAE/g) and from 0.82 to 5.44 mg quercetin equivalent (QE/g), respectively. The lowest IC50 for antioxidant and α-glucosidase inhibitory activities is presented by C. latifolia from a higher altitude region. Principal component analysis (PCA) from FTIR and UHPLC-Q-Orbitrap-HRMS data could discriminate the plant parts and geographical origin. Partial least squares (PLS) analysis has identified several functional groups, such as O-H, C-H, C=O, C-C, C-O, and chemical compounds, unknown-185 and unknown-85, that are most likely to contribute to the antioxidant and α-glucosidase inhibitory activities.

A mitochondrial protein homologous to the mammalian peripheral-type benzodiazepine receptor is essential for stress adaptation in plants.

The cloning of abiotic stress-inducible genes from the moss Physcomitrella patens led to the identification of the gene PpTSPO1, encoding a protein homologous to the mammalian mitochondrial peripheral-type benzodiazepine receptor and the bacterial tryptophane-rich sensory protein. This class of proteins is involved in the transport of intermediates of the tetrapyrrole biosynthesis pathway. Like the mammalian homologue, the PpTSPO1 protein is localized to mitochondria. The generation of PpTSPO1-targeted moss knock-out lines revealed an essential function of the gene in abiotic stress adaptation. Under stress conditions, the PpTSPO1 null mutants show elevated H(2)O(2) levels, enhanced lipid peroxidation and cell death, indicating an important role of PpTSPO1 in redox homeostasis. We hypothesize that PpTSPO1 acts to direct porphyrin precursors to the mitochondria for heme formation, and is involved in the removal of photoreactive tetrapyrrole intermediates.

Physcomitrella patens is highly tolerant against drought, salt and osmotic stress.

In order to determine the degree of tolerance of the moss Physcomitrella patens to different abiotic stress conditions, we examined its tolerance against salt, osmotic and dehydration stress. Compared to other plants like Arabidopsis thaliana, P. patens exhibits a high degree of abiotic stress tolerance, making it a valuable source for the identification of genes effecting the stress adaptation. Plants that had been treated with NaCl tolerated concentrations up to 350 mM. Treatments with sorbitol revealed that plants are able to survive concentrations up to 500 mM. Furthermore, plants that had lost 92% water on a fresh-weight basis were able to recover successfully. For molecular analyses, a P. patens expressed sequence tag (EST) database was searched for cDNA sequences showing homology to stress-associated genes of seed plants and bacteria. 45 novel P. patens genes were identified and subjected to cDNA macroarray analyses to define their expression pattern in response to water deficit. Among the selected cDNAs, we were able to identify a set of genes that is specifically up-regulated upon dehydration. These genes encode proteins exerting their function in maintaining the integrity of the plant cell as well as proteins that are known to be members of signaling networks. The identified genes will serve as molecular markers and potential targets for future functional analyses.