Oxidation pathways underlying the pro-oxidant effects of apigenin

Apigenin, a natural flavone, is emerging as a promising compound for the treatment of several diseases. One of the hallmarks of apigenin is the generation of intracellular reactive oxygen species (ROS), as judged by the oxidation of reduced dichlorofluorescein derivatives seen in many cell types. This study aimed to reveal some mechanisms by which apigenin can be oxidized and how apigenin-derived radicals affect the oxidation of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein (H₂DCF), a probe usually employed to detect intracellular ROS. Apigenin induced a rapid oxidation of H₂DCF in two different immortalized cell lines derived from rat and human hepatic stellate cells. However, apigenin did not generate ROS in these cells, as judged by dihydroethidium oxidation and extracellular hydrogen peroxide production. In cell-free experiments we found that oxidation of apigenin leads to the generation of a phenoxyl radical, which directly oxidizes H₂DCF with catalytic amounts of hydrogen peroxide. The net balance of the reaction was the oxidation of the probe by molecular oxygen due to redox cycling of apigenin. This flavonoid was also able to deplete NADH and glutathione by a similar mechanism. Interestingly, H₂DCF oxidation was significantly accelerated by apigenin in the presence of horseradish peroxidase and xanthine oxidase, but not with other enzymes showing peroxidase-like activity, such as cytochrome c or catalase. We conclude that in cells treated with apigenin oxidation of reduced dichlorofluorescein derivatives does not measure intracellular ROS and that pro- and antioxidant effects of flavonoids deduced from these experiments are inconclusive and must be confirmed by other techniques.     

Evaluation of andrographolide-based analogs derived from Andrographis paniculata against Mythimna separata Walker and Tetranychus cinnabarinus Boisduval

To discover new natural-product-based pesticides, we structurally modified andrographolide, a labdane diterpenoid isolated from Andrographis paniculata, and stereoselectively prepared a series of 12α-(substituted)benzylamino-14-deoxyandrographolide derivatives (I–V). Three-dimensional structures of compounds 3c, 3d, IIIa and IIIb were further determined by single-crystal X-ray diffraction. Compounds IIa (R¹ = n-C₃H₇, R² = PhCH₂) exhibited more promising insecticidal activity against Mythimna separata than toosendanin. Compounds 3a (R¹ = H), Ib (R¹ = H, R² = 4-ClPhCH₂), and IVa (R¹ = 4-ClPh, R² = PhCH₂) showed potent acaricidal activity against Tetranychus cinnabarinus.     

Flavonoid variation and evolution inAsplenium normale and related species (Aspleniaceae)

Flavonoid profiles of 132 populations (472 individuals) ofAsplenium normale, and related species,A. boreale, A. shimurae, andA. oligophlebium var.oligophlebium and var.iezimaense in Japan were surveyed by HPLC and 2D-PC. Of the five taxa, each ofAsplenium boreale, A. shimurae andA. oligophlebium including var.iezimaense had consistent flavonoid composition: apigenin 7, 4′-di-O-rhamnoside (9) inAsplenium boreale, 7-O-glucosyirhamnosides of apigenin and luteolin (6 and 7) inA. shimurae and genkwanin 4′-O-glucosyl-rhamnoside (5) in twoA. oligophlebium varieties. On the other hand,Asplenium normale was divided into seven chemotypes A-G: A-type has 7-O-dirhamnosides of apigenin and luteolin (1 and 2) and genkwanin 4′-O-glucosylrhamnoside (5); B-type, 5 alone; C-type, apigenin 7-O-rhamnoside-4′-O-glucosylrhamnoside (8); D-type, 1 and 2; E-type, 1,2 and 8; F-type, 1, 2, 5 and 8; and G-type, 5 and 8. Among them, the most frequent types were A, B and C, and A-type was mainly distributed in inland of Honshu, Shikoku and Kyushu, while B- and C-types extended their distribution areas southwards in general and occur along the Pacific coast with several exception. Chemical and evolutionary relationships amongAsplenium boreale, A. shimurae, A. oligophlebium, and the chemotypes ofA. normale were discussed on the basis of general biosynthetic pathway.     

Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from Scleropyrum pentandrum

Five unprecedented furan-2-carbonyl C-glycosides, scleropentasides A–E, and two phenolic diglycosides, 4-hydroxy-3-methoxybenzyl 4-O-β-d-xylopyranosyl-(1 → 6)-β-d-glucopyranoside and 2,6-dimethoxy-p-hydroquinone 1-O-β-d-xylopyranosyl-(1 → 6)-β-d-glucopyranoside, were isolated from leaves and twigs of Scleropyrum pentandrum together with potalioside B, luteolin 6-C-β-d-glucopyranoside (isoorientin), apigenin 8-C-β-d-glucopyranoside (vitexin), apigenin 6,8-di-C-β-d-glucopyranoside (vicenin-2), apigenin 6-C-α-l-arabinopyranosyl-8-C-β-d-glucopyranoside (isoschaftoside), apigenin 6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside, adenosine and l-tryptophan. Structure elucidations of these compounds were based on analyses of chemical and spectroscopic data, including 1D and 2D NMR. In addition, the isolated compounds were evaluated for their radical scavenging activities using both DPPH and ORAC assays.     

Phenolics from Tanacetum sinaicum (Fresen.) Delile ex Bremer & Humphries (Asteraceae)

The phytochemical investigation on Tanacetum sinaicum (Fresen.) Delile ex Bremer & Humphries led to the isolation of eight flavonoid aglycones (apigenin 1, acacetin 2, luteolin 3, chrysoeriol 4, cirsilineol 5, jaceidin 6, chrysosplenetin 7 and vitexicarpin; casticin 8), four flavonoid glycosides (apigenin 7-O-β-glucopyranoside 9, apigenin 7-O-β-glucuronide 10, luteolin 7-O-β-glucopyranoside 11 and luteolin 7-O-β-glucuronide 12) and three phenolics (4-hydroxy-3-methoxy benzoic acid 13, 3,4-dimethoxy benzoic acid 14 and 4-hydroxy acetophenone 15). Their structures were determined by chemical and spectroscopic analysis. Among them, compounds 1–3, 9, 11, 13 and 14 were reported for the first time from T. sinaicum. The chemotaxonomic significance of the isolated flavonoids was also summarized.     

Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids,acetylenic thiophenes and sesquiterpene lactones from Pluchea indica and Vernonia cinerea

The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1–4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5–8 from V. cinerea, and acetylenic thiophenes 9–11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic K_I values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32–15.4 and 0.92–8.67 µM, respectively, while those of thiophenes were 0.11–1.01 and 0.67–0.97 µM, respectively.     

Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity

By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.     

(2S)-Prenylflavanones and taraxerane triterpenoids from Mallotus mollissimus

Three prenylflavanones, (2S)-5,7-dihydroxy-4′-methoxy-8-(3″,3″-dimethylallyl)flavanone (3), (2S)-5,4′-dihydroxy-7-methoxy-6-(3″,3″-dimethylallyl)flavanone (6), 8-prenylnaringenin (11), and a new epimeric pair (2″S/2″R)-(2S)-5,7-dihydroxy-4′-methoxy-6-(2″-hydroxy-3″-methylbut-3″-enyl)flavanones (4a/4b) were isolated together with taraxerone, taraxerol, epitaraxerol, β-sitosterol, oleanolic acid, 1-O-docosanoyl glycerol, apigenin, and apigenin 7-O-β-D-glucopyranoside from the MeOH extract of the leaves of Mallotus mollissimus. The structures of the isolated compounds were determined on the basis of 1D/2D NMR and HR-MS spectroscopic data; the 2S configuration of the prenylflavanones 3, 4, and 6 was deduced from CD spectroscopic data. The presence of three taraxerane triterpenoids reinforces the inclusion of M. mollissimus (syn. Croton mollissimus) in Mallotus genus. Among species of Mallotus the occurrence of the (2S)-prenylflavanones 3, 4, and 6 is confined to M. mollissimus.     

Neuroprotective Effect of Apigenin on Depressive-Like Behavior: Mechanistic Approach

Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies proposed that apigenin affects depression disorder through unknown mechanistic pathways. The effects of apigenin’s anti-depressive properties on streptozocin-mediated depression have been investigated through the evaluation of behavioral tests, oxidative stress, cellular energy homeostasis and inflammatory responses. The results demonstrated anti-depressive properties of apigenin in behavioral test including forced swimming and splash tests and oxidative stress biomarkers such as reduced glutathione, lipid peroxidation, total antioxidant power and coenzyme Q₁₀ levels. Apigenin, also, demonstrated its regulatory potency in cellular energy homeostasis and immune system gene expression through inhibiting Nlrp3 and Tlr4 overexpression. Furthermore, failure in energy production as the key factor in various psychiatric disorders was reversed by apigenin modulating effect on AMPK gene expression. Overall, 20 mg/kg of apigenin was recognized as the dose suitable for minimizing the undesirable adverse effects in the STZ-mediated depression model proposed in this study. Our data suggested that apigenin could be able to adjust behavioral dysfunction, biochemical biomarkers and recovered cellular antioxidant level in depressed animals. The surprising results were achieved by raise in COQ₁₀ level, which could regulate the overexpression of the AMPK gene in stressful conditions. The regulatory effect of apigenin in inflammatory signaling pathways such as Nlrp3, and Tlr4 gene expression was studied at the surface part of the hippocampus.

     

IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3)

Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase vital to the regulation of T-cells. We report that JAK3 is a mediator of interleukin-8 (IL-8) stimulation of a different class of hematopoietic relevant cells: human neutrophils. IL-8 induced a time- and concentration-dependent activation of JAK3 activity in neutrophils and differentiated HL-60 leukemic cells. JAK3 was more robustly activated by IL-8 than other kinases: p70S6K, mTOR, MAPK or PKC. JAK3 silencing severely inhibited IL-8-mediated chemotaxis. Thus, IL-8 stimulates chemotaxis through a mechanism mediated by JAK3. Further, JAK3 activity and chemotaxis were inhibited by the flavonoid apigenin (4′,5,7-trihydroxyflavone) at ∼5 nM IC₅₀. These new findings lay the basis for understanding the molecular mechanism of cell migration as it relates to neutrophil-mediated chronic inflammatory processes.     

Stimulation of Mammalian G-protein-responsive Adenylyl Cyclases by Carbon Dioxide

Carbon dioxide is fundamental to the physiology of all organisms. There is considerable interest in the precise molecular mechanisms that organisms use to directly sense CO₂. Here we demonstrate that a mammalian recombinant G-protein-activated adenylyl cyclase and the related Rv1625c adenylyl cyclase of Mycobacterium tuberculosis are specifically stimulated by CO₂. Stimulation occurred at physiological concentrations of CO₂ through increased k_cat. CO₂ increased the affinity of enzyme for metal co-factor, but contact with metal was not necessary as CO₂ interacted directly with apoenzyme. CO₂ stimulated the activity of both G-protein-regulated adenylyl cyclases and Rv1625c in vivo. Activation of G-protein regulated adenylyl cyclases by CO₂ gave a corresponding increase in cAMP-response element-binding protein (CREB) phosphorylation. Comparison of the responses of the G-protein regulated adenylyl cyclases and the molecularly, and biochemically distinct mammalian soluble adenylyl cyclase revealed that whereas G-protein-regulated enzymes are responsive to CO₂, the soluble adenylyl cyclase is responsive to both CO₂ and bicarbonate ion. We have, thus, identified a signaling enzyme by which eukaryotes can directly detect and respond to fluctuating CO₂.Inorganic carbon (C_i)³ is central to prokaryotic and eukaryotic physiology. The predominant biologically active forms of C_i are CO₂ and and their relative contributions to the total C_i pool are pH-dependent. Biological roles for CO₂ and include photosynthetic carbon fixation (1), pH homeostasis (2), carbon metabolism (3), activation of virulence in pathogenic organisms (4), sperm maturation (5), and as an alarmone in Drosophila (6, 7).Given its importance in biology, the identification of CO₂ responsive signaling pathways is key to understanding how organisms cope with fluctuating CO₂. Two seven transmembrane receptors, Gr21a and Gr63a, have been shown to confer CO₂ responsiveness in Drosophila neurons (6, 7). Guanylyl cyclase D expressing olfactory neurons also mediate sensitivity to CO₂ in mice (8). A role for cGMP-activated channels in CO₂ sensing has been observed in CO₂ avoidance behavior in Caenorhabditis (9, 10). Despite these impressive advances, no eukaryotic signaling enzymes unequivocally demonstrated to respond to CO₂ have been identified.The mammalian soluble adenylyl cyclase (sAC) synthesizes the second messenger 3′,5′-cAMP and is directly stimulated by (11–13). Stimulation of sAC by has an unequivocal role in sperm maturation (5, 14–16). sAC is a member of the Class III family of adenylyl cyclases (ACs), a family that also includes the G-protein-regulated ACs and many examples from prokaryotic genomes (17, 18). The Class III ACs can be divided into four subclasses (a–d) based upon polymorphisms within the active site (19). sAC is a member of Class IIIb, a subclass characterized partly by replacement of a substrate binding Asp with Thr. The Class IIIa ACs include the mammalian G-protein-stimulated ACs and numerous prokaryotic examples. These have been previously assumed to be non-responsive to C_i (12).All prokaryotic Class IIIb ACs examined to date respond to C_i including enzymes from organisms as diverse as Anabaena PCC 7120, Mycobacterium tuberculosis, Stigmatella aurantiaca, and Chloroflexus aurantiacus (20, 21). Two Class IIIb ACs, Slr1991 of Synechocystis PCC 6803 and CyaB1 of Anabaena PCC 7120, have been proven to respond to CO₂ and not , giving rise to the idea of AC as a true gas-sensing molecule (22, 23). The finding that Class IIIb ACs respond to CO₂ and not necessitates an examination of the assumption that G-protein-regulated ACs and related prokaryotic enzymes do not respond to C_i.Here we demonstrate, contrary to previous work, that a recombinant G-protein-regulated AC and the Class IIIa Rv1625c AC of M. tuberculosis H37Rv show a pH-dependent response to C_i due to specific stimulation by CO₂ at physiologically relevant concentrations. CO₂ interacted directly with the apoprotein and modulated the activity of both the prokaryotic enzyme and G-protein-regulated AC in vivo. Finally, we contrasted the responses of sAC- and G-protein-regulated ACs to different species of C_i and propose that the mammalian cAMP signaling pathway is able to discriminate between CO₂ and in vivo.     

Sesquiterpene lactones,flavonoids and anthraquinones from Asphodeline globifera and Asphodeline Damascena

The known compounds chrysoeriol, apigenin, luteolin, acacetin, scutellarein, 6-methoxyluteolin, apigenin 7-glucoside, luteolin 7-glucoside, esculetin, chrysophanol, asphodeline, mircocarpin, sitosterol, 1-β-acetoxyeudesman-4(15),7(11)dien-2α,12-olide and 1-β-acetoxy-8β-hydroxyeudesman-4(15),7(11)-dien-8α,12-olide were isolated from Asphodeline globifera and A. damascena. A new sesquiterpene lactone 1-β-acetoxy-8β-ethoxyeudesman-4(15),7(11)dien-8α, 12-olide was also characterized. These are the first reports of sesquiterpene lactones in Asphodeline and in the Liliaceae.     

Microbial metabolism of prenylated apigenin derivatives by Mucor hiemalis

6-Prenylapigenin (1) and 8-prenylapegenin (2) were semi-synthesized from apigenin by nuclear prenylation. Morusin (3) was isolated from the root bark of Morus alba L. The microbial transformation studies of these three bioactive prenylated apigenin derivatives were performed using eighteen cell cultures in order to select microorganisms capable of transforming them. It was identified that Mucor hiemalis (KCTC 26779) showed the ability to metabolize the parent compounds (1–3) into three new (4–6) and one known (7) glucosylated derivatives with high efficiency. Their structures were established as 6-prenylapigenin 7-O-β-d-glucopyranoside (4), 8-prenylapigenin 7-O-β-d-glucopyranoside (5), morusin 5-O-β-d-glucopyranoside (6), and morusin 4′-O-β-d-glucopyranoside (7) by the spectroscopic methods.     

Constituents of the leaves of Pseuderanthemum carruthersii (Seem.) Guill. var. atropurpureum (Bull.) Fosb.

A new iridoid, 5β,6β-dihydroxyantirrhide (1) was isolated from the dried leaves of Pseuderanthemum carruthersii (Seem.) Guill. var. atropurpureum (Bull.) Fosb. (Acanthaceae), together with 13 known compounds, including two iridoids, linarioside and antirrhinoside; five phenylethanoids, echipuroside A, verbascoside, isoverbascoside, isomartynoside and osmanthuside B; and six flavonoids, luteolin 7-O-β-d-glucopyranoside, luteolin 7-O-rutinoside, apigenin 7-O-rutinoside, apigenin 6-C-α-l-arabinopyranosyl–8-C-β-l-arabinopyranoside, apigenin 6,8-di-C-α-l-arabinopyranoside and apigenin 6-C-β-d-xylopyranosyl–8-C-α-l-arabinopyranoside. Their chemical structures were elucidated by 1D and 2D NMR as well as HR-ESI-MS spectroscopic analysis. Some purified compounds were evaluated the acetylcholinesterase inhibition and cytotoxic activities against the HeLa cervical cancer cell line and the MCF-7 breast cancer cell line at the concentration of 100 μg/mL. Luteolin 7-O-β-d-glucopyranoside exhibited cytotoxic activities against both the HeLa cervical cancer cell line and the MCF-7 breast cancer cell line. Verbascoside and isoverbascoside showed strong cytotoxic activity against the MCF-7 breast cancer cell line. The tested compounds showed the AChE inhibitory activity fairly weak.     

Chemotaxonomic value of flavonoids in Chromolaena congesta (Asteraceae)

The phytochemical investigation on the aerial parts of Chromolaena congesta led to the isolation of nine flavonoids, known in the literature as genkwanin (1) kumatakenin (2) acacetin (3), kaempferol 3-methyl ether (4), apigenin (5), apigenin 5,7-dimethyl ether (6), apigenin 5-methyl ether (7), luteolin (8) and kaempferol (9). The chemical structures were established on the basis of spectral evidence. All the compounds were isolated from this species for the first time. The results from the present study provide further information about the flavonoids as taxonomic marker of the genus Chromolaena, and the chemotaxonomic significance of these compounds were also summarized.     

Genomic organization of the extracellular coding region of the human FGFR4 and FLT4 genes: Evolution of the genes encoding receptor tyrosine kinases with immunoglobulin-like domains

Receptor tyrosine kinases with five, seven, and three Ig-like domains in their extracellular region are grouped in subclasses IIIa, IIIb, and IIIc, respectively. Here, we describe the genomic organization of the extracellular coding region of the human FGFR4 (IIIc) and FLT4 (IIIb) genes and compare it to that of the human FGFR1(IIIc), KIT, and FMS (IIIa). The results show that while genes belonging to the same subclass have an identical exon/intron structure in their extracellular coding region—as they do in their intracellular coding region—genes of related subclasses only have a similar exon/intron structure. These results strongly support the hypothesis that the genes of the three subclasses evolved from a common ancestor by duplications involving entire genes, already in pieces. Hypotheses on the origin of introns and on the difference in the number of extracellular Ig-like domains in the three gene subclasses are discussed. Received: 19 August 1996 / Accepted: 2 January 1997     

Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages

Background

Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood.

Methodology and Principal Findings

In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB.

Conclusion and Significance

Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases.     

Association of Fc gamma-receptor genes polymorphisms with chronic periodontitis and Peri-Implantitis

This study was conducted on 87 patients with chronic periodontitis (CP), 50 patients with peri-implantitis and 90 periodontally healthy individuals referring to the Department of Periodontics for evaluating the association between Fc gamma-receptor genes polymorphisms with CP and peri-implantitis. After obtaining consent, venous blood samples (5cc) were obtained from patients and DNA was extracted using Miller's salting-out method. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system-PCR methods were used to assess the polymorphisms of FcγRs IIa, IIIa, and IIIb genes. Analyzing showed a significant association between specific genotypes with increasing CP and peri-implantitis risks in codominant and dominant models. For FcγR IIIa, analyzing revealed a significant association between specific genotypes with increasing CP and peri-implantitis risks in codominant, dominant, and recessive models. For FcγR IIIb, we also detected a significant association between specific genotypes with increasing CP and peri-implantitis risks in codominant, dominant, and recessive models ( P < 0.05). According to the results of this study, the FCGRIIa (rs1801274), FCGRIIIa (rs396991), and FCGRIIIb (rs1050501) polymorphisms were significantly associated with CP and peri-implantitis and may have a role in the pathogenesis of these diseases.     

Secondary Metabolites and Antimycobacterial Activities from the Roots of Ficus nervosa

Bioassay‐guided fractionation of the active AcOEt‐soluble layer led to the isolation of two new pyranocoumarins, 3‐hydroxyxanthyletin ( 1 ) and 3‐methoxyxanthyletin ( 2 ), along with 22 known compounds including four simple coumarins, i.e., xanthyletin ( 3 ), umbelliferone ( 4 ), scopoletin ( 5 ), and (+)‐(S)‐marmesin ( 6 ); nine flavonoids, i.e., carpachromene ( 7 ), parvisoflavone B ( 8 ), alpinumisoflavone ( 9 ) genistein ( 10 ), 2′‐hydroxygenistein ( 11 ), prunetin ( 12 ), cajanin ( 13 ), apigenin ( 14 ), and (2S)‐naringenin ( 15 ); three benzenoids, i.e., 4‐hydroxybenzaldehyde ( 16 ), vanillin ( 17 ), and (S)‐lasiodiplodin ( 18 ); five steroids, i.e., ergosterol peroxide ( 19 ), a mixture of 6β‐hydroxystigmast‐4‐en‐3‐one ( 20 ) and 6β‐hydroxystigmasta‐4,22‐dien‐3‐one ( 21 ), and a mixture of β‐sitosterol ( 22 ) and stigmasterol ( 23 ); and one triterpenoid, i.e., oleanolic acid ( 24 ) from the roots of Ficus nervosa. Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR as well as MS analyses. Among these isolates, 3‐hydroxyxanthyletin ( 1 ), genistein ( 10 ), prunetin ( 12 ), and (2S)‐naringenin ( 15 ) showed antimycobacterial activities against Mycobacterium tuberculosis H₃₇R_V in vitro with MIC values of 16, 35, 30, and ≤2.8 μg/ml, respectively.