Multi-target drugs for the treatment of cognitive impairment and fatigue in post-COVID syndrome: focus on Ginkgo biloba and Rhodiola rosea.

Cognitive impairment, depression and (mental) fatigue represent the most frequent neuropsychiatric symptoms of the post-COVID syndrome. Neuroinflammation, oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological mechanisms underlying these symptoms. Attempts to treat post-COVID-associated cognitive impairment and fatigue with different drugs available for other diseases have not yet been successful. One probable explanation could be that these drugs work by one specific mechanism of action only and not in a broad multi-target way. Therefore, they will not address the broad pathophysiological spectrum possibly responsible for cognitive impairment, depression and fatigue in post-COVID syndrome. Notably, nearly all drugs currently under investigation for fatigue in post-COVID syndrome are rather addressing one single target instead of the several pathomechanisms underlying this condition. Contrary to this approach, herbal drugs often consist of many different ingredients with different pharmacological properties and pharmacological targets. Therefore, these drugs might be a promising approach for the treatment of the broad symptomatic presentation and the pathophysiological mechanisms of cognitive impairment and fatigue following a SARS-CoV-2 infection. Of these herbal drugs, extracts of Ginkgo biloba and Rhodiola rosea probably are the best investigated candidates. Their broad pharmacological spectrum in vitro and in vivo includes anti-oxidative, anti-inflammatory, antidepressant as well as properties reducing cognitive impairment and fatigue. In several studies, both drugs showed positive effects on physical and mental fatigue and impaired cognition. Moreover, depressive symptoms were also reduced in some studies. However, even if these results are promising, the data are still preliminary and require additional proof by further studies.

Rhodiola rosea L. improved intestinal digestive enzyme activities, inflammatory response, barrier and microbiota dysbiosis in Lateolabrax maculatus juveniles fed with high-carbohydrate diets.

A 56-d feeding trial was conducted to evaluate the influences of Rhodiola rosea L. on digestive enzyme activities, intestinal barrier, inflammatory response, and microbiota dysbiosis in Lateolabrax maculatus juveniles (9.37 ± 0.03 g) fed with high-carbohydrate diets. Six diets were designed: a control diet (20% corn starch, Control), high-carbohydrate diet (30% corn starch, HC1), and four high-carbohydrate diets supplemented with Rhodiola rosea L. at 30, 60, 90 and 120 mg/kg (HC2, HC3, HC4 and HC5, respectively). Compared with the control group, the HC1 diet remarkably increased α-amylase, lipase, and chymotrypsin activities in the intestine (p < 0.05), as well as the mRNA levels of Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 (p < 0.05) and the relative abundance of Proteobacteria and Photobacterium in the intestine, which belong to the phylum and genus level, respectively. But the opposite trend was found in muscular thickness and villus lengths (p < 0.05), the mRNA levels of Occludin, ZO-1, and TGF-ß (p < 0.05), at the level of phylum and genus level in the HC1 group, and the relative abundance of Firmicutes, Bacteroidetes, and Bacillus in the intestine compared with the control group. Intestinal chymotrypsin activity was significantly higher in the HC3 group and intestinal muscular thickness and villus lengths were also significantly higher in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). In addition, Occludin mRNA expression in the intestine was significantly increased in the HC2, HC4, and HC5 groups compared to the HC1 group. ZO-1 and TGF-ß mRNA expression in the intestine were significantly increased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was higher in the intestine in the HC2, HC3, HC4, and HC5 groups than that in the HC1 group. On the contrary, intestinal lipase and chymotrypsin activities were significantly decreased in the HC2 group compared to the HC1 group, respectively (p < 0.05). The Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 mRNA expression in the intestine were significantly decreased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). Besides, at the genus level, compared to the HC1 group, the relative abundance of Photobacterium in the intestine and the diversity of the intestinal microbiota in the HC2, HC3, HC4, and HC5 groups were all decreased. In conclusion, these results demonstrated that the addition of Rhodiola rosea L. in high-carbohydrate diets can improve intestinal digestive enzyme activities, inflammatory response and intestinal barrier-related gene expression, and microbiota dysbiosis in L. maculatus. The suitable supplemental level of Rhodiola rosea L. in high-carbohydrate diets of L. maculatus is 60 mg/kg.

Immediate and residual effects of functional chewing gum on sustained attention and mood.

Objectives: Chewing gum has been shown to improve aspects of cognition and mood with sustained attention being particularly receptive to the effects of chewing. Chewing gum may also be a useful vehicle for administering functional ingredients. The herbal extract Rhodiola rosea and certain B-vitamins have previously been shown to improve aspects of cognition and subjective state, but their combined effects have not been studied to date.Methods: The current randomised, placebo-controlled, double-blind, balanced crossover study compared the effects of a functional gum containing Rhodiola rosea and B-vitamins to flavour-matched regular chewing gum and a flavour-matched placebo. Thirty-six healthy young participants completed measures of attention and mood at baseline, during chewing, and 1-h after chewing.Results: Chewing both functional and regular gum was shown to reduce errors on a digit vigilance task compared to placebo irrespective of whether measured during or after chewing. There were no benefits to adding functional ingredients to the gum.Discussion: Future chewing research should consider different formats of placebo. Sex differences in response to chewing and the impact of rate and intensity of chewing should also be explored.Trial registration: ClinicalTrials.gov identifier: NCT05544500.

Therapeutic Promises of Bioactive Rosavin: A Comprehensive Review with Mechanistic Insight.

Rosavin is an alkylbenzene diglycoside primarily found in Rhodiola rosea (L.), demonstrating various pharmacological properties in a number of preclinical test systems. This study focuses on evaluating the pharmacological effects of rosavin and the underlying molecular mechanisms based on different preclinical and non-clinical investigations. The findings revealed that rosavin has anti-microbial, antioxidant, and different protective effects, including neuroprotective effects against various neurodegenerative ailments such as mild cognitive disorders, neuropathic pain, depression, and stress, as well as gastroprotective, osteoprotective, pulmoprotective, and hepatoprotective activities. This protective effect of rosavin is due to its capability to diminish inflammation and oxidative stress. The compound also manifested anticancer properties against various cancer via exerting cytotoxicity, apoptotic cell death, arresting the different phases (G0/G1) of the cancerous cell cycle, inhibiting migration, and invading other organs. Rosavin also regulated MAPK/ERK signaling pathways to exert suppressing effect of cancer cell. However, because of its high-water solubility, which lowers its permeability, the phytochemical has low oral bioavailability. The compound's relevant drug likeness was evaluated by the in silico ADME, revealing appropriate drug likeness. We suggest more extensive investigation and clinical studies to determine safety, efficacy, and human dose to establish the compound as a reliable therapeutic agent.

Neuromodulatory Effects Induced by the Association of Moringa oleifera Lam., Tribulus terrestris L., Rhodiola rosea Lam., and Undaria pinnatidifida Extracts in the Hypothalamus.

The present study investigated the role of a commercial formulation constituted by herbal extracts from Rhodiola rosea, Undaria pinnatifida, Tribulus terrestris, and Moringa oleifera. The formulation was analysed for determining the content in total phenols and flavonoids and scavenging/reducing properties. The formulation was also tested on isolated mouse hypothalamus in order to investigate effects on serotonin, dopamine, neuropeptide Y (NPY), and orexin A. The gene expression of gonadrotopin releasing hormone (GnRH) was also assayed. The formulation was able to reduce dopamine and serotonin turnover, and this could be related, albeit partially, to the capability of different phytochemicals, among which hyperoside and catechin to inhibit monoaminooxidases activity. In parallel, the formulation was effective in reducing the gene expression of NPY and orexin-A and to improve the gene expression of GnRH. In this context, the increased GnRH gene expression induced by the formulation may contribute not only to improve the resistance towards the stress related to ageing, but also to prevent the reduction of libido that could be related with a stimulation of the serotoninergic pathway. According to the in silico analysis, hyperoside could play a pivotal role in modulating the gene expression of GnRH. Regarding NPY and orexin A gene expression, no direct interactions between the formulation phytochemicals and these neuropeptides were anticipated; thus, suggesting that the pattern of gene expression observed following exposure of the hypothalamus to the formulation may be secondary to inhibitory effects of dopamine and serotonin turnover. Concluding, the present study demonstrated the efficacy of the formulation in exerting neuromodulatory effects at the hypothalamic level; thus, suggesting the potential to contrast stress and fatigue.

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Effects of Fermentation with Kombucha Symbiotic Culture of Bacteria and Yeasts on Antioxidant Activities, Bioactive Compounds and Sensory Indicators of Rhodiola rosea and Salvia miltiorrhiza Beverages.

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review.

Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They are found in many traditional medicinal systems and play a key role in restoring the body's strength and stamina. Research in recent years has attempted to elucidate the mechanisms behind their pharmacological effects, but it appears that these effects are difficult to define precisely and involve multiple molecular pathways. Neuroinflammation: In recent years, chronic inflammation has been recognized as one of the common features of many central nervous system disorders (dementia and other neurodegenerative diseases, depression, anxiety, ischemic stroke, and infections). Because of the specific nature of the brain, this process is called neuroinflammation, and its suppression can result in an improvement of patients' condition and may promote their recovery. Adaptogens as anti-inflammatory agents: As has been discovered, adaptogens display anti-inflammatory effects, which suggests that their application may be broader than previously thought. They regulate gene expression of anti- and proinflammatory cytokines (prostaglandins, leukotriens) and can modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims to present the anti-neuroinflammatory potential of the most important plants classified as adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea and Withania somnifera.

Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects. OBJECTIVE: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI. MATERIALS AND METHODS: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 µg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 µg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation. RESULTS: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 µg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results. DISCUSSION AND CONCLUSION: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

A conserved gene regulatory network controls root epidermal cell patterning in superrosid species.

In superrosid species, root epidermal cells differentiate into root hair cells and nonhair cells. In some superrosids, the root hair cells and nonhair cells are distributed randomly (Type I pattern), and in others, they are arranged in a position-dependent manner (Type III pattern). The model plant Arabidopsis (Arabidopsis thaliana) adopts the Type III pattern, and the gene regulatory network (GRN) that controls this pattern has been defined. However, it is unclear whether the Type III pattern in other species is controlled by a similar GRN as in Arabidopsis, and it is not known how the different patterns evolved. In this study, we analyzed superrosid species Rhodiola rosea, Boehmeria nivea, and Cucumis sativus for their root epidermal cell patterns. Combining phylogenetics, transcriptomics, and cross-species complementation, we analyzed homologs of the Arabidopsis patterning genes from these species. We identified R. rosea and B. nivea as Type III species and C. sativus as Type I species. We discovered substantial similarities in structure, expression, and function of Arabidopsis patterning gene homologs in R. rosea and B. nivea, and major changes in C. sativus. We propose that in superrosids, diverse Type III species inherited the patterning GRN from a common ancestor, whereas Type I species arose by mutations in multiple lineages.

Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases.

The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer's and Parkinson's diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.

Application of Natural Deep Eutectic Solvents for Extraction of Bioactive Components from Rhodiola rosea (L.).

Rhodiola rosea (L.) is a valuable source of nutrients. Nutrients have adaptogenic, immunostimulating, nootropic, anti-inflammatory and anti-cancer properties. Natural deep eutectic solvents (NADES) consisting of choline chloride and malonic, malic, tartaric or citric acids have been first used to extract biologically active substances from R. rosea. The total content of polyphenols has been determined by the Folin-Ciocalteu method for all extracts. Antioxidant activity has been determined by the phosphomolybdate method, and antiradical activity has been determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Rosavin concentration has been determined by high-performance liquid chromatography (HPLC). Extraction kinetics has been evaluated regarding the effectiveness of NADES with each other and with reference solvents (water and 50% ethanol) has been made. Extraction conditions have been optimized according to the Box-Behnken design of the experiment. The optimal parameters of the extraction process have been established. The antibacterial activity of NADES-based extracts against bacterial cultures of Micrococcus luteus, Pseudomonas fluorescens, and Bacillus subtilis has been studied.

Rosavin: Research Advances in Extraction and Synthesis, Pharmacological Activities and Therapeutic Effects on Diseases of the Characteristic Active Ingredients of Rhodiola rosea L.

Rhodiola rosea L. (RRL) is a popular plant in traditional medicine, and Rosavin, a characteristic ingredient of RRL, is considered one of the most important active ingredients in it. In recent years, with deepening research on its pharmacological actions, the clinical application value and demand for Rosavin have been steadily increasing. Various routes for the extraction and all-chemical or biological synthesis of Rosavin have been gradually developed for the large-scale production and broad application of Rosavin. Pharmacological studies have demonstrated that Rosavin has a variety of biological activities, including antioxidant, lipid-lowering, analgesic, antiradiation, antitumor and immunomodulation effects. Rosavin showed significant therapeutic effects on a range of chronic diseases, including neurological, digestive, respiratory and bone-related disorders during in vitro and vivo experiments, demonstrating the great potential of Rosavin as a therapeutic drug for diseases. This paper gives a comprehensive and insightful overview of Rosavin, focusing on its extraction and synthesis, pharmacological activities, progress in disease-treatment research and formulation studies, providing a reference for the production and preparation, further clinical research and applications of Rosavin in the future.

Bioactivity Profiles on 15 Different Effect Mechanisms for 15 Golden Root Products via High-Performance Thin-Layer Chromatography, Planar Assays, and High-Resolution Mass Spectrometry.

Planar chromatography has recently been combined with six different effect-directed assays for three golden root (Rhodiola rosea L.) samples. However, the profiles obtained showed an intense tailing, making zone differentiation impossible. The profiling was therefore improved to allow for the detection of individual bioactive compounds, and the range of samples was extended to 15 commercial golden root products. Further effect-directed assays were studied providing information on 15 different effect mechanisms, i.e., (1) tyrosinase, (2) acetylcholinesterase, (3) butyrylcholinesterase, (4) ß-glucuronidase, and (5) α-amylase inhibition, as well as endocrine activity via the triplex planar yeast antagonist-verified (6-8) estrogen or (9-11) androgen screen, (12) genotoxicity via the planar SOS-Umu-C bioassay, antimicrobial activity against (13) Gram-negative Aliivibrio fischeri and (14) Gram-positive Bacillus subtilis bacteria, and (15) antioxidative activity (DPPH• radical scavengers). Most of the golden root profiles obtained were characteristic, but some samples differed substantially. The United States Pharmacopeia reference product showed medium activity in most of the assays. The six most active compound zones were further characterized using high-resolution mass spectrometry, and the mass signals obtained were tentatively assigned to molecular formulae. In addition to confirming the known activities, this study is the first to report that golden root constituents inhibit butyrylcholinesterase (rosin was tentatively assigned), ß-glucuronidase (rosavin, rosarin, rosiridin, viridoside, and salidroside were tentatively assigned), and α-amylase (stearic acid and palmitic acid were tentatively assigned) and that they are genotoxic (hydroquinone was tentatively assigned) and are both agonistic and antagonistic endocrine active.

The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions-Encouraging Clinical Evidence.

Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.

Protective effect of salidroside on streptozotocin-induced diabetic nephropathy by inhibiting oxidative stress and inflammation in rats via the Akt/GSK-3ß signalling pathway.

CONTEXT: Salidroside (SAL), one of the major glycosides isolated from the roots of Rhodiola rosea L. (Crassulaceae), has anti-inflammatory, antioxidant, and antidiabetic properties. OBJECTIVE: Our study assessed whether SAL exerts a protective effect on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via the Akt/GSK-3ß signalling pathway. MATERIALS AND METHODS: Adult male Wistar rats were divided into three groups (n = 8): normal control, DN + vehicle, and DN + SAL. SAL (50 mg/kg/day, oral) was administered for 8 weeks. Biochemical and histopathologic examinations were performed to evaluate the therapeutic effects of SAL on oxidative stress, inflammation, renal function, and apoptosis. RESULTS: SAL induced rats demonstrated ameliorated levels of FBG (20.53 ± 0.72 mmol/L vs. 26.02 ± 1.44 mmol/L), urine albumin excretion (27.00 ± 1.46 mmol/L vs. 41.00 ± 1.59 mmol/L), blood urea nitrogen (14.42 ± 0.70 mmol/L vs. 17.77 ± 0.72 mmol/L), and serum creatinine (112.80 ± 6.98 mmol/L vs. 159.00 ± 3.81 mmol/L) compared to normal control rats, along with the alleviation of renal pathologic changes by improving the irregular shape of glomeruli tissues. Biochemical analysis showed that SAL-treated animals displayed suppressed levels of serum inflammatory cytokines and kidney oxidative stress markers and attenuated apoptotic characteristics. Moreover, it increased the phosphorylation levels of Akt and GSK-3ß in kidneys. DISCUSSION AND CONCLUSION: The present study validated the involvement of the Akt/GSK-3ß signalling pathway in renal improvement. These findings can form the basis to investigate the protective effect of SAL in DN in clinical trials.

Rhodiola rosea polysaccharides promote the proliferation of bone marrow haematopoietic progenitor cells and stromal cells in mice with aplastic anaemia.

CONTEXT: The effects of Rhodiola rosea L. (Crassulaceae) polysaccharides (RRPs) on haematopoiesis are poorly understood. OBJECTIVE: To determine the effects of RRPs on haematopoiesis in mice with aplastic anaemia. MATERIALS AND METHODS: Aplastic anaemia was induced in Kunming mice by 60Coγ (2.0 Gy) irradiation and cyclophosphamide administration (50 mg/kg/day for 3 consecutive days; intraperitoneal injection). The in vivo effects of RRPs (10, 20, and 40 mg/kg; intraperitoneal injection) on haematopoiesis were analyzed using peripheral blood tests, histopathological examination of haematopoietic tissues, culture of haematopoietic progenitors and bone marrow stromal cells (BMSCs), and Western blotting of Fas and Fas ligand (FasL). The in vitro effects of RRPs on bone-marrow haematopoietic progenitors and BMSCs were also evaluated. RESULTS: Compared to anaemic controls, high-dose RRPs (40 mg/kg) significantly increased red blood cells (8.21 ± 0.57835 versus 6.13 ± 1.34623 × 1012/L), white blood cells (5.11 ± 1.6141 versus l.54 ± 1.1539 × 109/L), and BMSCs (10.33 ± 1.5542 versus 5.87 ± 3.1567 × 1012/L) in mice with aplastic anaemia (all p < 0.01). High-dose RRPs significantly increased the formation of colony-forming unit-granulocyte macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E; p < 0.01). Fas and FasL protein expression in BMSCs decreased after RRPs administration. Especially at the high dose, RRPs (150 µg/mL) significantly promoted in vitro CFUs-E, BFUs-E, and CFUs-GM formation. RRPs (150-300 µg/mL) also promoted BMSC proliferation. DISCUSSION AND CONCLUSIONS: RRPs helped to promote haematopoietic recovery in mice with aplastic anaemia, facilitating haematopoietic tissue recovery. This study indicated some mechanisms of the haematopoietic regulatory effects of RRPs. Our findings provide a laboratory basis for clinical research on RRPs.

A supercritical fluid workflow for the quality assessment of herbal drugs and commercial preparations from Rhodiola rosea.

INTRODUCTION: Preparations from the Rhodiola rosea are experiencing an increase in popularity: extracts of dried roots and rhizomes are used as adaptogen to treat stress, fatigue, and weakness. To meet high pharmaceutical standards, fast and reliable methods to assess phytochemical variations in respect of quality control are needed. OBJECTIVE: The aim of this study was to extract and quantify seven characteristic secondary metabolites of R. rosea, namely p-tyrosol (1), rosin (2), rosiridin (3), salidroside (4), rosarin (5), rosavin (6), and tricin-5-O-ß-d-glucopyranoside (7) in 24 herbal drugs and seven commercial preparations using a newly established supercritical fluid workflow. METHODS: The developed protocol allowed for an exhaustive extraction of compounds 1-7 using 60% carbon dioxide (CO2 ) and 40% methanol. The constituents were analysed on an ultra-high-performance supercritical fluid chromatography (UHPSFC) instrument using a charged surface hybrid fluoro-phenyl (CSH FP) column (3.0 mm × 100 mm, 1.7 µm; mobile phase: CO2 and methanol). RESULTS: The seven compounds were separated in a remarkably short time (< 3.5 minutes). For their quantitation, good results in terms of selectivity, linearity (R2 ≥ 0.99), precision (intraday ≤ 3.03%, interday ≤ 5.17%) and accuracy (recovery rates 96.6-102.4%) were achieved using selected ion recording on a Quadrupole Dalton (QDa) mass detector. CONCLUSION: The quantitative analysis of the investigated herbal drugs showed a highly differing metabolite pattern which was also observed in the investigated commercial products. None of the commercial dietary products met the declared content of rosavins and salidroside. The developed and validated protocol offers a novel and reliable method to assess the quantitative composition of Rhodiola herbal drugs and preparations.

Long-term toxicological studies on the Chinese medicine 2036 Specialty-Qiangxin recipe in rats.

CONTEXT: The traditional medicine 2036 Specialty-Qiangxin recipe (2036S-QXR) has been widely used in China to improve cardiac function, prevent stroke, and strengthen the immune system. However, its long-term toxicity remains unknown. OBJECTIVE: The present study evaluates the long-term toxicity of 2036S-QXR in rats. MATERIALS AND METHODS: 2036S-QXR (0.6, 1.2, and 2.4 g/kg body weight per day) was orally administered for 26 weeks to Wistar rats, while the rats in the control group received distilled water. The effects on urinary, hematological, biochemical, and histopathological parameters were investigated during the study period. RESULTS: No significant changes in all tested parameters were observed in the 0.6 and 1.2 g/kg groups, compared with the control group (p < 0.05). Higher levels of alanine aminotransferase (46.00 ± 12.85 vs. 25.40 ± 3.36) and aspartate aminotransferase (152.40 ± 32.52 vs. 111.40 ± 18.78) were observed after 13 weeks in the female rats in the 2.4 g/kg group compared with the control group (p < 0.05), but these returned to the control levels after the recovery period (p > 0.05). Several cases displayed the presence of urine protein (3/7 males and 3/7 females) and mild lesions in the kidney (10/20) and thymus (5/20) in the 2.4 g/kg group, without significant changes compared with the control group (p > 0.05). DISCUSSION AND CONCLUSIONS: The present study shows that 2036S-QXR does not cause long-term toxicity, supporting its therapeutic use. To further determine the optimal doses, future studies should test more doses and include more animals in each group.

Can the biological mechanisms of ageing be corrected by food supplementation. The concept of health care over sick care.

"From care for the sick to care for health" implies that age-related diseases and discomforts, which impair the quality of life, should be prevented rather than treated. Healthy lifestyle and nutrition, and hormone supplementation - when needed - are of crucial importance. Food supplementation with nutraceuticals composed of vitamins, oligo-minerals, plant extracts and essential amino- and fatty acids should reduce age-related oxidative and epigenetic damage to DNA, and inhibit inflammatory and metabolic impairment. This study of the potential beneficial effects of novel nutraceuticals on the biological mechanisms of physical and mental ageing suggests these supplements may be scientifically justified. In the absence of adverse side effects and the expected favourable effect on the quality-adjusted life years, the benefit over risk ratio of nutraceutical supplementation should be positive.