Endophytic fungus Penicillium steckii DF33 promoted tanshinones biosynthesis in Salvia miltiorrhiza by regulating the expression of CYP450 genes.

Salvia miltiorrhiza, a prominent traditional Chinese medicinal resource, has been extensively employed in the management of cardiovascular and cerebrovascular ailments. Ensuring the consistency of S. miltiorrhiza raw materials revolves around the imperative task of maintaining stable tanshinones content and composition. An effective approach in this regard involves the utilization of endophytic fungi as inducers. Within this context, our study spotlights an endophytic fungus, Penicillium steckii DF33, isolated from the roots of S. miltiorrhiza. Remarkably, this fungus has demonstrated a significant capacity to boost the biosynthesis and accumulation of tanshinones. The primary objective of this investigation is to elucidate the underlying regulatory mechanism by which DF33 enhances and regulates the biosynthesis and accumulation of tanshinones. This is achieved through its influence on the differential expression of crucial CYP450 genes within the S. miltiorrhiza hairy roots system. The results revealed that the DF33 elicitor not only promotes the growth of hairy roots but also enhances the accumulation of tanshinones. Notably, the content of cryptotanshinone was reached 1.6452 ± 0.0925 mg g-1, a fourfold increase compared to the control group. Our qRT-PCR results further demonstrate that the DF33 elicitor significantly up-regulates the expression of most key enzyme genes (GGPPS, CPS1, KSL1, CYP76AH1, CYP76AH3, CYP76AK1, CYP71D411) involved in the tanshinone biosynthesis pathway. This effect is particularly pronounced in certain critical CYP450 genes and Tanshinone ⅡA synthase (SmTⅡAS), with their expression levels peaking at 7 days or 14 days, respectively. In summary, endophytic P. steckii DF33 primarily enhances tanshinone biosynthesis by elevating the expression levels of pivotal enzyme genes associated with the modification and transformation stages within the tanshinone biosynthesis pathway. These findings underscore the potential of employing plant probiotics, specifically endophytic and root-associated microbes, to facilitate the biosynthesis and transformation of vital constituents in medicinal plants, and this approach holds promise for enhancing the quality of traditional Chinese medicinal materials.

Insight into the antioxidant activities of ten Fabaceae plant species that are medicinally used by the Aucan Tribal Peoples from the Republic of Suriname (South America).

Fabaceae are associated with a high antioxidant activity (AA) and a high total phenolic (TPC), total flavonoid (TFC), and selenium content (SeC). In this study, the aqueous extracts from ten Fabaceae species that are medicinally used by the Aucan Tribal Peoples from Suriname (South America), were evaluated for AA using a DPPH and a FRAP assay, and for TPC, TFC, and SeC using Folin-Ciocalteu's, an AlCl3 colorimetric, and an azure B-based method. Associations between pairs of these variables were determined by Pearson correlation coefficient. One-way ANOVA with post-hoc Tukey's test was used to evaluate the data for statistically significant differences (p < 0.05). The I. stipularis (bark), C. guyanensis (bark), A. jupunba (twigs), and M. urens (fruit) extracts had the highest DPPH IC50 values (36 - 70 µg/mL) and FRAP values (346 - 573 µM FeE/100 µg) and the highest TPC (25 - 41 GAEq/100 µg), TFC (21 - 39 REq/100 µg), and SeC (4 -17 µg/g). The values for the T. indica (leaf), P. macroloba (bark), M. pigra (whole plant), S. quinquangulata (leaf), A. sensitiva (whole plant), and L. leucocephala (leaf) extracts were > 10-fold lower. AA, TPC, TFC, and SeC correlated well with each other (correlation coefficient ≥ 0.83, p ≤ 0.0030). Thus, AA, TPC, TFC, and SeC may represent important determinants of the health benefits of the former four samples but not of the others. Future studies should focus on the precise contribution of AA, TPC, TFC, and SeC to the therapeutic value of medicinal Fabaceae.

Single-Arm Resistance Training Study to Determine the Relationship between Training Outcomes and Muscle Growth Factor mRNAs in Older Adults Consuming Numerous Medications and Supplements.

OBJECTIVES: Determine if the muscle mRNA levels of three growth factors (insulin-like growth factor-1 [IGF1], ciliary neurotropic factor [CNTF], and vascular endothelial growth factor-D [VEGFD]) are correlated with muscle size and strength gains from resistance exercise while piloting a training program in older adults taking medications and supplements for age-associated problems. DESIGN: Single-arm prospective study. SETTING: US Veterans Affairs hospital. PARTICIPANTS: Older (70±6 yrs) male Veterans (N=14) of US military service. INTERVENTION: Thirty-five sessions of high-intensity (80% one-rep max) resistance training including leg press, knee curl, and knee extension to target the thigh muscles. MEASUREMENTS: Vastus lateralis biopsies were collected and body composition (DEXA) was determined pre- and post-training. Simple Pearson correlations were used to compare training outcomes to growth factor mRNA levels and other independent variables such as medication and supplement use. RESULTS: Average strength increase for the group was ≥ 25% for each exercise. Subjects averaged taking numerous medications (N=5±3) and supplements (N=2±2). Of the growth factors, a significant correlation (R>0.7, P≤0.003) was only found between pre-training VEGFD and gains in lean thigh mass and extension strength. Mass and strength gains were also correlated with use of α-1 antagonists (R=0.55, P=0.04) and pre-training lean mass (R=0.56, P=0.04), respectively. CONCLUSIONS: Muscle VEGFD, muscle mass, and use of α-1 antagonists may be predisposing factors that influence the response to training in this population of older adults but additional investigation is required to determine if these relationships are due to muscle angiogenesis and blood supply.

Beneficial effect of medicinal plants on the contractility of post-hypoxic isolated guinea pig atria - Potential implications for the treatment of ischemic-reperfusion injury.

Context Ischemic-reperfusion injury is accompanied by a decreased contractility of the myocardium. Positive-inotropic agents have proven useful for treating this condition but may exert serious side-effects. Objective In this study, aqueous preparations from Abelmoschus esculentus L. Moench (Malvaceae), Annona muricata L. (Annonaceae), Bixa orellana L. (Bixaceae), Cecropia peltata L. (Moraceae), Erythrina fusca Lour. (Fabaceae), Psidium guajava L. (Myrtaceae) and Terminalia catappa L. (Combretaceae) were evaluated for their ability to improve the decreased contractility of isolated guinea pig atria after hypoxic stress. Materials and methods Guinea pig atria isolated in Ringer-Locke buffer gassed with 100% O2 at 30 °C were exposed for 5 min to hypoxia, then allowed to recover in oxygenated buffer alone or containing a single plant extract (0.001-1 mg/mL). The contractility (g/s) and beating frequency (beats/min), as well as troponin C contents of the bathing solution (ng/mL), were determined and expressed as means ± SDs. Results The extracts of A. muricata, B. orellana, C. peltata and T. catappa caused an increase in the contractility compared to untreated atria of 340 ± 102%, 151 ± 13%, 141 ± 14% and 238 ± 44%, respectively. However, the latter two preparations increased the troponin C contents of the bathing solution to 36 ± 11 and 69 ± 33, compared to the value of 11 ± 3 ng/mL found with untreated atria. Conclusions Preparations from A. muricata and B. orellana may possess positive-inotropic properties which may improve the contractility of the post-hypoxic myocardium. Studies to assess their usefulness in ischemic-reperfusion injury are warranted.