Scientific and Regulatory Approach to Botanical Drug Development: A U.S. FDA Perspective

Wu, Chao‐Liang; Su-Lin, Lee; Taylor, Cassandra; Li, Jing; Chan, Yen-Ming; Agarwal, Rajiv; Temple, Robert; Throckmorton, Douglas C.; Tyner, Katherine M.

doi:10.1021/acs.jnatprod.9b00949

Cited by 63 publications

(78 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In cases where synergy is found in plant extracts, options such as the FDA Botanical Drug Guidance exist for the development of whole extracts or refined fractions as drugs (FDA, 2016). Two botanical drugs have been approved by the FDA: Veregen (sinecatechins), a green tea extract (Camellia sinensis (L.) Kuntze, Theaceae) for the treatment of genital and perianal warts, and Fulyzaq or Mytesi (crofelemer) from the dragon's blood tree (Croton lechleri Müll.Arg., Euphorbiaceae), used to treat diarrhea associated with HIV anti-retroviral therapy (Wu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

et al. 2021

View full text Add to dashboard Cite

Background: Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s’ golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted.Objectives: This systematic review aims to evaluate reports on plants with significant antibacterial activities.Methods: Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: “plant,” “antibacterial,” “inhibitory concentration.”Results: We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while Cinnamomum verum, Rosmarinus vulgaris and Thymus vulgaris were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally, Staphylococcus aureus was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature.Conclusion: This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.

show abstract

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nowadays, plant-based medicines have been playing an important role in drug discovery and development. They are also widely employed in various public health practices as they are safe, cost-effective, and possess unique chemical diversity [ 1 , 2 ]. Cancer remains one of the leading causes of death globally, with approximately 18.1 million new cases and 9.6 million cancer-related deaths in 2018, according to the World Health Organization [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Preliminary Biological Activity Screening of Plectranthus spp. Extracts for the Search of Anticancer Lead Molecules

et al. 2021

View full text Add to dashboard Cite

Plectranthus species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen Plectranthus acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract was screened against yeasts, and Gram-positive and Gram-negative bacteria. The P. hadiensis and P. mutabilis extracts possessed significant activity against Staphylococcus aureus and Candida albicans (microdilution method). Moreover, all extracts showed antioxidant activity using the DPPH method, with P. hadiensis and P. mutabilis extracts having the highest scavenging activities. Selected by the Artemia salina model, P. hadiensis and P.ciliatus possessed low micromolar anti-proliferative activities in human colon, breast, and lung cancer cell lines. Furthermore, the most bioactive extract of P. hadiensis leaves and the known abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone isolated from this plant, were tested against the aggressive type triple negative breast cancer (MDA-MB-231S). P. hadiensis extract reduced the viability of MDA-MB-231S cancer cell line cells, showing an IC50 value of 25.6 µg/mL. The IC50 value of 7α-acetoxy-6β-hydroxyroyleanone was 5.5 µM (2.15 µg/mL), suggesting that this lead molecule is a potential starting tool for the development of anti-cancer drugs.

show abstract

“…As mentioned above, our inference is that multiple compounds contribute to the dual selectivity of BT extract. However, in fact, this is the fundamental of traditional herbal medicine: more than one component contributes to the overall therapeutic effect, and some components may not have therapeutic activities but are required for the combinatory effects [42,43]. To possess dual-selective NRF2 regulation function in cells with different regulatory contexts of the NRF2 pathway, the candidate must have the ability to modulate at least two distinct mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Identification of Beilschmiedia tsangii Root Extract as a Liver Cancer Cell–Normal Keratinocyte Dual-Selective NRF2 Regulator

et al. 2021

View full text Add to dashboard Cite

Transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in regulating the expression of genes participating in cellular defense mechanisms against oxidative or xenobiotic insults. However, there is increasing evidence showing that hyperactivation of NRF2 is associated with chemoresistance in several cancers, including hepatocellular carcinoma (HCC), thus making NRF2 an attractive target for cancer therapy. Another important issue in cancer medication is the adverse effects of these substances on normal cells. Here, we attempted to identify a dual-selective NRF2 regulator that exerts opposite effects on NRF2-hyperactivated HCC cells and normal keratinocytes. An antioxidant response element driven luciferase reporter assay was established in Huh7 and HaCaT cells as high-throughput screening platforms. Screening of 3,000 crude extracts from the Taiwanese Indigenous Plant Extract Library resulted in the identification of Beilschmiedia tsangii (BT) root extract as a dual-selective NRF2 regulator. Multiple compounds were found to contribute to the dual-selective effects of BT extract on NRF2 signaling in two cell lines. BT extract reduced NRF2 protein level and target gene expression levels in Huh7 cells but increased them in HaCaT cells. Furthermore, notable combinatory cytotoxic effects of BT extract and sorafenib on Huh7 cells were observed. On the contrary, sorafenib-induced inflammatory reactions in HaCaT cells were reduced by BT extract. In conclusion, our results suggest that the combination of a selective NRF2 activator and inhibitor could be a practical strategy for fine-tuning NRF2 activity for better cancer treatment and that plant extracts or partially purified fractions could be a promising source for the discovery of dual-selective NRF2 regulators.

show abstract

Scientific and Regulatory Approach to Botanical Drug Development: A U.S. FDA Perspective

Cited by 63 publications

References 16 publications

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

Preliminary Biological Activity Screening of Plectranthus spp. Extracts for the Search of Anticancer Lead Molecules

Identification of Beilschmiedia tsangii Root Extract as a Liver Cancer Cell–Normal Keratinocyte Dual-Selective NRF2 Regulator

Contact Info

Product

Resources

About