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Toward enhanced hyperforin production in St. John's wort root cultures.

ABSTRACT: During the past decades, several trials targeted a stable, sustainable and economic production of St. John's wort (Hypericum perforatum) extract. The value of this extract stems from its use to treat depression and skin irritation due to its hyperforin content. Previously, hyperforin-forming in vitro root cultures were established. Here, detailed growth and production kinetics have been analyzed over 40 days of cultivation. In the first 10 days, sucrose was completely hydrolyzed to glucose and fructose. The ammonium consumption supported the increase in the biomass and hyperforin production. When sucrose was replaced with glucose/fructose, the linear growth phase started 6 days earlier and resulted in a higher space-time-yield. The maximum hyperforin production was 0.82 mg L-1 day-1, which was 67 % higher than in the sucrose-supplemented standard cultivation. Buffering the sucrose-supplemented medium with phosphate caused a 2.7-fold increase in the product to biomass yield coefficient. However, the combination of monosaccharides and buffering conditions did not cause an appreciable improvements in the production performance of the shake flask approaches. A potential scalability from flask to lab-scale stirred bioreactors has been demonstrated. The results obtained offer a basis for a scalable production of hyperforin and a sustainable source for a tissue culture-based phytomedicine.

SUBMITTER: Gaid M

PROVIDER: S-EPMC6999061 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Toward enhanced hyperforin production in St. John's wort root cultures.

Gaid Mariam M Grosch Jan-Hendrik JH Möller Steve S Beerhues Ludger L Krull Rainer R

Engineering in life sciences 20190604 12

During the past decades, several trials targeted a stable, sustainable and economic production of St. John's wort (<i>Hypericum perforatum</i>) extract. The value of this extract stems from its use to treat depression and skin irritation due to its hyperforin content. Previously, hyperforin-forming <i>in vitro</i> root cultures were established. Here, detailed growth and production kinetics have been analyzed over 40 days of cultivation. In the first 10 days, sucrose was completely hydrolyzed to ...[more]

PMID: 32624982

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Project description:BACKGROUND:In some countries extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) are widely used for treating patients with depressive symptoms. OBJECTIVES:To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs. SEARCH STRATEGY:Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers. SELECTION CRITERIA:Trials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John's wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms. DATA COLLECTION AND ANALYSIS:At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects. MAIN RESULTS:A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83). AUTHORS' CONCLUSIONS:The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Project description:BACKGROUND: St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. METHODS: Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. RESULTS: Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0-8) for 23.9% completeness. CONCLUSION: The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.

Project description:Background: Saint John's wort (Hypericum perforatum L., HP) is commonly registered in Europe under the THR scheme (Traditional Herbal Registration) or licensed as a medicine. Nonetheless unregulated medical products and food supplements are accessible through the internet which are often of poor quality. The species' natural distribution stretches through large regions of Europe to China and four subspecies have been distinguished. When compared to the European Pharmacopoeia reference, the presence of additional compounds was linked to so-called Chinese HP. Aim: In order to obtain an integrated picture of the entire chemoprofile, the chemical composition of HP materia prima was studied using a combination of techniques well-established in the relevant industries. The impact of phytogeographic factors on the materia prima can shed light on whether the variability of the final products is strongly influenced by these factors of whether they relate to poor processing, adulteration, or other factors linked to the processing of the material. Methods: Eighty-six Hypericum samples (77 H. perforatum) were collected from 14 countries. Most were authenticated and harvested in the wild; others came as roughly ground material from commercial cultivations, markets and pharmacies. The samples were analyzed using HPTLC and 1H-NMR-based principal component analysis (PCA). Results and Discussion: Limited chemical variability was found. Nonetheless, the typical fingerprint of Chinese HP was observed in each specimen from China. Additional compounds were also detected in some samples collected in Spain. Rutin is not necessarily present in the crude material. The variability previously found in the marketed products can be ascribed only partially to the geographical origin of harvested material, but mainly to the plant part harvested, closely related to harvesting techniques, processing and probably time of harvest. Conclusion: HP can be sourced in a consistent composition (and thus quality) from different geographical sources. However, chemical variability needs to be accounted for when evaluating what is considered authentic good material. Therefore, the processing and good practice are all stages of primary importance, calling for a better (self-)regulation and quality assurance along the value chain of an herbal medical product or botanical.

Dataset Information

Toward enhanced hyperforin production in St. John's wort root cultures.

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Toward enhanced hyperforin production in St. John's wort root cultures.

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