Obtaining a robust phylogeny proves challenging due to the intricate evolutionary history of species, where processes such as hybridization and incomplete lineage sorting can introduce conflicting signals, thereby complicating phylogenetic inference. In this study, we conducted comprehensive sampling of Elsholtzieae, with a particular focus on its largest genus, Elsholtzia. We utilized 503 nuclear loci and complete plastome sequences obtained from 99 whole-genome sequencing datasets to elucidate the interspecific relationships within the Elsholtzieae. Additionally, we explored various sources of conflicts between gene trees and species trees. Fully supported backbone phylogenies were recovered, and the monophyly of Elsholtzia and Keiskea was not supported. Significant gene tree heterogeneity was observed at numerous nodes, particularly regarding the placement of Vuhuangia and the E. densa clade. Further investigations into potential causes of this discordance revealed that incomplete lineage sorting (ILS), coupled with hybridization events, has given rise to substantial gene tree discordance. Several species, represented by multiple samples, exhibited a closer association with geographical distribution rather than following a strictly monophyletic pattern in plastid trees, suggesting chloroplast capture within Elsholtzieae and providing evidence of hybridization. In conclusion, this study provides phylogenomic insights to untangle taxonomic problems in the tribe Elsholtzieae, especially the genus Elsholtzia.

BACKGROUND: Elsholtzia belongs to the Labiatae family, which consists of herbaceous subshrubs and shrubs. Among them, volatile oils are an important chemical component in Elsholtzia, which have various bioactive medicinal and developmental values.
METHODS: The references about volatile oils of Elsholtzia in this review were obtained from Web of Science, SciFinder, PubMed, Willy, Elsevier, SpringLink, ACS publications, Google Scholar, Baidu Scholar, Scopus, and CNKI. The other information about Elsholtzia was obtained from classical works or ancient books.
RESULTS: Traditionally, the volatile oils from Elsholtzia were used in Chinese medicine to treat cholera, abdominal pain, vomiting, and scattered edema. Relevant research revealed that Elsholtzia contains many different types of volatile oils, and most of them display bioactivities, including anti-oxidant, anti-bacterial, anti-viral, hypolipidemic, insecticidal, and antiinflammatory activities, treating spleen and stomach. Furthermore, the applications of volatile oils were summarized and analyzed in this paper.
CONCLUSIONS: The contents of traditional use, constituent analysis, bioactivity, and application of volatile oils from Elsholtzia were reviewed in this paper. This will provide important research value and a scientific basis for the in-depth study of the plants of Elsholtzia in the future.

BACKGROUND: Elsholtzia is a genus in the family Lamiaceae, and some species in this genus are commonly used for food and in ethnomedicinal formulations by some ethnic groups of China and Thailand. Despite their apparent utility, few studies have been conducted to evaluate their potential as sources of medicinally active agents.
OBJECTIVE: We aimed to investigate the cytotoxicity of ethanolic extracts from three selected edible plant species of the genus Elsholtzia and the most promising extract was further characterized for the bioactive constituents and signaling mechanisms associated with the anti-leukemic activity.
METHODS: Ethanolic extracts were screened for cytotoxicity using flow cytometry. HPLC and LC-MS were used to analyze the chemical constituents of the most potent fraction from E. stachyodes. The relevant mechanism of action was assessed by western blot and multispectral imaging flow cytometry (MIFC).
RESULTS: The most potent anti-leukemic activity was observed with the ethanolic extract from E. stachyodes. Luteolin and apigenin were characterized as the major constituents in the fraction from E. stachyodes. Mechanistically, the luteolin-apigenin enriched fraction (LAEF) induced the UPR, increased autophagic flux, induced cell cycle arrest and apoptotic cell death. LAEF showed significantly less cytotoxicity towards peripheral blood mononuclear cells (PBMCs) as compared to leukemia cell lines.
CONCLUSIONS: This study is the first to report E. stachyodes as a new source of luteolin and apigenin which are capable of triggering leukemic cell death. This could lead to a novel strategy against leukemia using ethnomedicinal plant extracts as an alternative or supplemental anti-cancer agent.

We sequenced the leaf and inflorescence transcriptomes of 10 Elsholtzia species to mine genes related to the volatile terpenoid metabolic pathway. A total of 184.68 GB data and 1,231,162,678 clean reads were obtained from 20 Elsholtzia samples, and 333,848 unigenes with an average length of at least 1440 bp were obtained by Trinity assembly. KEGG pathway analysis showed that there were three pathways related to volatile terpene metabolism: terpenoid backbone biosynthesis (No. ko00900), monoterpenoid biosynthesis (No. ko00902), and sesquiterpenoid and triterpenoid biosynthesis (No. ko00909), with 437, 125, and 121 related unigenes, respectively. The essential oil content and composition in 20 Elsholtzia samples were determined by gas chromatography-mass spectrometry. The results showed that there were obvious interspecific differences among the 10 Elsholtzia species, but there were no significant differences between the different tissues among species. The expression levels of seven candidate genes involved in volatile terpenoid biosynthesis in Elsholtzia were further analyzed by quantitative real-time PCR. The results showed that HMGS had the highest expression among all genes, followed by GGPS4. In addition, there was not a significant correlation between the seven genes and the components with high essential oil contents. Combined with the essential oil components detected in this study, the possible biosynthetic pathway of the characteristic components in Elsholtzia plants was speculated to be a metabolic pathway with geraniol as the starting point and elsholtzione as the end product. Phylogenetic analysis was conducted using the nucleotide sequences of the geranyl diphosphate synthase candidate genes, and the results showed that genes related to the volatile terpenoid biosynthetic pathway may be more suitable gene fragments for resolving the Elsholtzia phylogeny.

BACKGROUND: The genus Elsholtzia (family Labiaceae) is an important source of folk traditional Chinese medicine, mainly used to relieve the symptoms of cold, fever, pneumonia and so on. However, currently available data on its traditional and pharmacological advantages have not been comprehensively reviewed.
OBJECTIVE: This review provides up-to-date and comprehensive information on the ethnopharmacological, phytochemical, pharmacological properties and toxicity of Elsholtzia, highlights the antibacterial, antiviral, and anti-inflammatory advantages of the genus, and explores its therapeutic potential.
METHODS: Use Google Scholar, Scifinder, PubMed, Springer, Elsevier, Wiley, Web of Science and other online database search to collect the research literatures on application, chemistry and biological activity of Elsholtzia published before December 2021. Their scientific names have been verified using The Plant List and World Flora Online websites.
RESULTS: A total of 42 species of Elsholtzia are widely distributed all over the world, especially in Yunnan Province (China). Since Elsholtzia genus is commonly used in the folk to treat respiratory infectious diseases such as cold and fever, growing numbers of studies have confirmed their antiviral, antibacterial and anti-inflammatory activities. So far, about 221 non-volatile compounds and 1008 volatile compounds have been identified from Elsholtzia plants, mainly containing flavonoids and terpenoids showing convincing antibacterial, antiviral and anti-inflammatory activities. Further research found that their antibacterial and antiviral spectrums are broad, and volatile oils are considered to be the main antibacterial components. Their anti-inflammatory mechanism is mainly through the inhibition of NF-κB and MAPKs signaling pathways. Toxicological studies have not established its toxicity.
CONCLUSIONS: By summarizing the latest information on genus Elsholtzia, their traditional uses, material basis and mechanisms of action in antiviral, antibacterial and anti-inflammatory aspects were described, providing new insights for the genus and its importance as a potential natural resource of antiviral and anti-inflammatory drugs, giving evidence and new ideas for the development of herbal medicines.

The objective of this experimental study was to examine the effects of the Chinese herbal medicines Patchouli and Elsholtzia on the follicular granulosa cells of hens undergoing heat stress conditions. In the current investigation, hen follicular granulosa cells were isolated from the prehierarchical follicles of layer hens and then cultured in-vitro. The cells were randomly divided into the 6 groups. Following the completion of this study\'s experiments using different heat stress and medicinal treatments, the cell activities of each group were measured using an MTT method. The levels of the heat shock protein 70 (HSP70) were detected using ELISA. The expressions of the steroidogenic acute regulatory protein (StAR) mRNA; cytochrome P450 family 11, subfamily A, member 1 (CYP11A1) mRNA; proliferating cell nuclear antigen (PCNA) mRNA; and the follicle stimulating hormone receptor (FSHR) were detected using the real-time quantitative polymerase chain reactions. The concentration levels of estrogen and progesterone in the cell supernatant of each group were measured using ELISA. The results showed that cell activity had significantly decreased following the heat stress treatments at 43℃, 44℃, and 45℃ (P < 0.01), respectively. Meanwhile, cell activities observed in Patchouli and Elsholtzia were found to be much better than those of heat stress group (P < 0.05). In addition, the expression levels of HSP70 in the follicular granulosa cells of Patchouli and Elsholtzia groups were lower than those of heat stress group. Patchouli and Elsholtzia can maintain expressions of the receptor at 43℃. This study determined that the estrogen and progesterone in the supernatant fluid of Patchouli and Elsholtzia were higher than those observed in heat stress. Therefore, the results obtained in this study indicated that the Patchouli and Elsholtzia treatments administered prior the heat stress experiments had successfully protected the follicular granulosa cells from heat damages while maintaining the normal secretory functions of the granulosa cells.