A review of typical biological activities of glycyrrhetinic acid and its derivatives.

Glycyrrhetinic acid, a triterpenoid compound primarily sourced from licorice root, exhibits noteworthy biological attributes, including anti-inflammatory, anti-tumor, antibacterial, antiviral, and antioxidant effects. Despite these commendable effects, its further advancement and application, especially in clinical use, have been hindered by its limited druggability, including challenges such as low solubility and bioavailability. To enhance its biological activity and pharmaceutical efficacy, numerous research studies focus on the structural modification, associated biological activity data, and underlying mechanisms of glycyrrhetinic acid and its derivatives. This review endeavors to systematically compile and organize glycyrrhetinic acid derivatives that have demonstrated outstanding biological activities over the preceding decade, delineating their molecular structures, biological effects, underlying mechanisms, and future prospects for assisting researchers in finding and designing novel glycyrrhetinic acid derivatives, foster the exploration of structure-activity relationships, and aid in the screening of potential candidate compounds.

Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-c]quinazolinone Derivatives Targeting Potential Cyclin-Dependent Kinases.

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 µM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors.

Stimuli-responsive electrospun nanofibers for drug delivery, cancer therapy, wound dressing, and tissue engineering.

The stimuli-responsive nanofibers prepared by electrospinning have become an ideal stimuli-responsive material due to their large specific surface area and porosity, which can respond extremely quickly to external environmental incitement. As an intelligent drug delivery platform, stimuli-responsive nanofibers can efficiently load drugs and then be stimulated by specific conditions (light, temperature, magnetic field, ultrasound, pH or ROS, etc.) to achieve slow, on-demand or targeted release, showing great potential in areas such as drug delivery, tumor therapy, wound dressing, and tissue engineering. Therefore, this paper reviews the recent trends of stimuli-responsive electrospun nanofibers as intelligent drug delivery platforms in the field of biomedicine.

A Potential Anti-Glioblastoma Compound LH20 Induces Apoptosis and Arrest of Human Glioblastoma Cells via CDK4/6 Inhibition.

Glioblastoma (GBM) is a deadly brain tumor characterized by signaling dysregulation and aberrant cell cycle control. The CDK4/6-Rb axis is dysregulated in approximately 80% of all GBM cases. In this study, the anti-GBM effect of a novel pyrimidin-2-amine, LH20 was evaluated in vitro using the primary GBM cell lines U87MG and U251. GBM cells were administered LH20 at concentrations of 0.1, 1, 4, 8, 10, 20, 100, and 200 µM for 24 and 48 h, and the proliferation rate was evaluated using a CCK8 assay. Migration, apoptosis, and cell cycle were also assessed using a wound healing assay, Annexin V-FITC/PI apoptosis assay, and cell cycle staining, respectively. The targets of LH20 were predicted using SwissTargetPrediction and molecular docking. Western blotting analysis was performed to confirm the anti-GBM mechanism of LH20. We found that at concentrations of 4, 8, and 10 µM, LH20 significantly inhibited the proliferation and migration of U87MG and U251 cells, induced late phase apoptosis, promoted tumor cell necrosis, and arrested the G2/M phase of the cell cycle. LH20 also inhibited CDK4 and CDK6 activities by decreasing the phosphorylation of Rb. Our results suggest LH20 as a potential treatment strategy against GBM.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Intelligent Nanotransducer for Deep-Tumor Hypoxia Modulation and Enhanced Dual-Photosensitizer Photodynamic Therapy.

Upconversion nanoparticles (UCNPs) emerged as promising near-infrared (NIR) light-triggered nanotransducers for photodynamic therapy (PDT). However, the traditionally used 980 nm excitation source could cause an overheating effect on biological tissues, and the single photosensitizer (PS) loading could not efficiently utilize multiradiation UC luminescence, resulting in a limited efficiency of PDT in tumor tissues with hypoxia characteristics. Herein, 808 nm light-responsive Nd-sensitized UCNPs@mSiO2@MnO2 core-shell NPs were designed as light nanotransducers with efficient UC emission at 550 and 650 nm for PDT and downshifting luminescence at 1525 nm for second NIR (NIR-II) imaging. UC emission was fully utilized by loading dual PSs, rose bengal (RB), and zinc phthalocyanine (ZnPc), thus significantly improving the reactive oxide species (ROS) generation efficiency. Moreover, a manganese dioxide (MnO2) shell with ultrasensitive biodegradability in an acidic tumor microenvironment (TME) can generate an amount of oxygen molecules, alleviating the symptoms of hypoxia and then improving the efficacy of PDT. Meanwhile, the biodegraded Mn2+ ions can further strengthen T1-weighted magnetic resonance imaging (MRI). This work presented a new multifunctional theranostic agent for combining NIR-II/MRI imaging and 808 nm light-triggered PDT to combat the limitations of cancer therapy.

In Vivo High-Resolution Bioimaging of Bone Marrow and Fracture Diagnosis Using Lanthanide Nanoprobes with 1525 nm Emission.

Bones play vital roles in human health. Noninvasive visualization of the full extent of bones is highly demanded to evaluate many bone-related diseases. Herein, we report poly (acrylic acid) (PAA)-modified NaLuF4:Yb/Er/Gd/Ce@NaYF4 nanoparticles (PAA-Er) with second near-infrared emission beyond 1500 nm (also referred as NIR-IIb) for high-resolution bone/bone marrow imaging and bone fracture diagnosis. The NIR-IIb optical-guided bone marrow imaging presents a high signal to noise ratio, which is superior to that for imaging in the NIR-II window (1000-1400 nm, NIR-IIa). Importantly, we also investigated the size-dependent accumulation of the nanoparticles and the possible accumulation mechanism of the designed PAA-Er nanoprobes in bone marrow. Due to the high affinity capability of the PAA-Er nanoprobes, a highly sensitive NIR-IIb optical-guided bone fracture diagnosis was successfully achieved. This novel technology paves the way to design lanthanide nanoprobes for NIR-IIb optical-guided high-resolution bone marrow imaging and bone-related disease diagnosis.

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants.

Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting technology, possess customized structure and strength. The addition of a growth factor coating to the scaffold introduces a specific form of biological activation. Vascular endothelial growth factor (VEGF) is key to angiogenesis and osteogenesis in vivo. We designed a porous titanium alloy scaffold/thermosensitive collagen hydrogel system, equipped with VEGF, to promote local osseointegration and angiogenesis. We also verified the VEGF release via thermosensitive collagen and proliferation and induction of the human umbilical vein endothelial cells (HUVECs) via the composite system in vitro. In vivo, using microscopic computed tomography (Micro-CT), histology, and immunohistochemistry analysis, we confirmed that the composite scaffold aids in angiogenesis-mediated bone regeneration, and promotes significantly more bone integration. We also discovered that the composite scaffold has excellent biocompatibility, provides bioactive VEGF for angiogenesis and osteointegration, and provides an important theoretical basis for the restoration of local blood supply and strengthening of bone integration.

Soft X-Ray Stimulated Lanthanide@MOF Nanoprobe for Amplifying Deep Tissue Synergistic Photodynamic and Antitumor Immunotherapy.

Combining photodynamic therapy (PDT) and immunotherapy has shown profound impact for synergistic treatment of malignant tumors. However, the shallow penetration depth of the traditional visible light activated PDT, immunosuppressive tumor microenvironment (TME), and poor immunogenicity of deep-seated solid tumors have significantly impeded the therapeutic efficiency. Herein, a soft X-ray activated nanoprobe is rationally engineered via integrating porphyrin Zr-based metal-organic framework with lanthanide NaYF4 :Gd,Tb@NaYF4 scintillator nanoparticles (SNPs) by a new in situ growth strategy for synergistic PDT and immunotherapy of tumor. The nanoprobe possesses remarkably enhanced reactive oxygen species (ROS) generation triggered by soft X-ray via further covalently grafting rose bengal on the nanoprobe, even at tissue depths of 3 cm. Moreover, the soft X-ray induced ROS can act as potential immunogenic cell death (ICD) trigger, subsequently leading to the activation of the adaptive antitumor immune-response. Significantly, the boosted ROS generation can further modulate the immunosuppressive TME. This work provides new strategy of designing antitumor nanoprobes for soft X-ray triggered deep-tissue PDT and immune response, breaking the depth barriers suffered by the traditional photoactivated PDT or ICD using visible and near infrared light.

Low Dose Soft X-Ray Remotely Triggered Lanthanide Nanovaccine for Deep Tissue CO Gas Release and Activation of Systemic Anti-Tumor Immunoresponse.

Gas-based therapy has emerged as a new green therapy strategy for anti-tumor treatment. However, the therapeutic efficacy is still restricted by the deep tissue controlled release, poor lymphocytic infiltration, and inherent immunosuppressive tumor microenvironment (TME). Herein, a new type of nanovaccine is designed by integrating low dose soft X-ray-triggered CO releasing lanthanide scintillator nanoparticles (ScNPs: NaLuF4 :Gd,Tb@NaLuF4 ) with photo-responsive CO releasing moiety (PhotoCORM) for synergistic CO gas/immuno-therapy of tumors. The designed nanovaccine presents significantly boosted radioluminescence and enables deep tissue CO generation at unprecedented tissue depths of 5 cm under soft X-ray irradiation. Intriguingly, CO as a superior immunogenic cell death (ICD) inducer further reverses the deep tissue immunosuppressive TME and concurrently activates adaptive anti-tumor immunity through efficient reactive oxygen species (ROS) generation. More importantly, the designed nanovaccine presents efficient growth inhibition of both local and distant tumors via a soft X-ray activated systemic anti-tumor immunoresponse. This work provides a new strategy of designing anti-tumor nanovaccines for synergistic deep tissue gas-therapy and remote soft X-ray photoactivation of the immune response.

A general strategy for designing NIR-II emissive silk for the in vivo monitoring of an implanted stent model beyond 1500 nm.

Silk fibroin-based materials spun by silkworms present excellent biocompatible and biodegradable properties, endowing them with broad applications for use in in vivo implanted devices. Therefore, it is highly desirable to explore functionalized silk with additional optical bioimaging abilities for the direct in situ monitoring of the status of implanted devices in vivo. Herein, a new type of silk material with a second near-infrared (NIR-II, 1000-1700 nm) emission is explored for the real-time observation of a biological stent model using a general route of feeding larval silkworms with lanthanide-based NaYF4:Gd3+/Yb3+/Er3+@SiO2 nanocrystals. After being fed lanthanide nanocrystals, the silk spun by silkworms shows efficient NIR-II emission beyond 1500 nm. Moreover, NIR-II bio-imaging guided biological stent model monitoring presents a superior signal-to-noise (S/N) ratio compared to the traditional optical imaging by utilizing the upconversion (UC) region. These findings open up the possibility of designing NIR-II optically functionalized silk materials for highly sensitive and deep-tissue monitoring of the in vivo states of the implanted devices.

Endogenous H2S-Triggered In Situ Synthesis of NIR-II-Emitting Nanoprobe for In Vivo Intelligently Lighting Up Colorectal Cancer.

Overexpression of endogenous H2S is one of the key characteristic in colon cancer. However, developing endogenous H2S-activated optical probes for specific diagnosis of colorectal cancer is rarely explored. Herein, an in situ H2S-activatable second near-infrared (NIR-II)-emitting nanoprobe based on Ag-chicken egg white (Ag-CEW) complex for intelligently lighting up colorectal cancer was explored. The designed Ag-CEW complex holds efficient NIR-II emission of 1,000-1,400 nm via endogenous H2S-induced in situ chemical reaction to form Ag2S quantum dots (QDs). After reaction, the designed Ag-CEW complex with high photo-stability and biocompatibility was successfully used for NIR-II imaging-guided specific visualization and precise location of colorectal cancer via endogenous H2S activation. Therefore, our findings provide a new route for specifically targeting diagnosis of colon cancer based on the in situ-activatable NIR-II probe.

808 nm laser-triggered NIR-II emissive rare-earth nanoprobes for small tumor detection and blood vessel imaging.

Optical bioimaging in second near-infrared window (NIR-II, 1000-1700 nm) has been emerged as an indispensable tool for highly sensitive disease detection. In this work, intense NIR-II emissive polyacrylic acid (PAA) modified NaLuF4: Gd/Nd nanorods (PAA-NRs) with pure hexagonal phase and uniform size were explored for high sensitivity in vivo NIR-II bioimaging and optical imaging-guided small tumor detection. The NIR-II emission of the NaLuF4: Gd host can be readily adjusted by doping Nd3+, making it promising emission centered at 1056 nm and 1328 nm with high photo-stability. The time-dependent in vivo tracking results validate that the PAA-NRs are mainly accumulated in the reticuloendothelial system (RES) and excreted through the hepatic pathway. In addition, NIR-II optical imaging-guided small tumor (down to 5 mm) diagnosis was successfully achieved. Remarkably, in vivo small blood vessel with high spatial resolution (~105 µm) was detected clearly. And the histological tests reveal that our designed hydrophilic NRs present negligible toxicity effects and good biocompatibility in living animals. Besides the NIR-II emission, the PAA-NRs also present X-ray absorption features for X-ray bioimaging. These findings demonstrate that the explored lanthanide-based NRs with controllable size, efficient NIR-II emission and decent biocompatibility are promising NIR-II contrast agents for future biomedical applications, such as, early diagnosis of small tumor, vascular related disease imaging and angiogenesis diagnosis.

Theranostic Carbon Dots with Innovative NIR-II Emission for in Vivo Renal-Excreted Optical Imaging and Photothermal Therapy.

Carbon dots (CDs) with low biotoxicity, high photostability, and well-controlled size are highly desirable imaging agents for optical bioimaging. However, most of the CDs triggered by ultraviolet/blue light present visible/first near-infrared emissions shorter than 820 nm, impairing their imaging applications in vivo by low penetration depth. Hence, developing novel CD-based materials with second near-infrared (NIR-II) emission located in 1000-1700 nm region is an urgent task. Here, a novel NIR-II-emitting CD-based nanoprobe triggered by 808 nm laser is developed. The designed CDs with 900-1200 nm luminescence possess high quantum yield (QY-0.4%) and high biocompatibility, which have proven to be effective probes for in vivo NIR-II bioimaging. Notably, nearly 65% CDs are excreted from mouse urine within 6 h, demonstrating the rapid renal clearance of CDs. Furthermore, the designed CDs also exhibit high photothermal efficiency (30.6%), making them ideal materials for thermal ablation of cancer. Our findings pave the way of designing a multifunctional CD-based theranostic platform for simultaneously integrating the advanced NIR-II bioimaging and photothermal therapy of cancer.

Non-Invasive Optical Guided Tumor Metastasis/Vessel Imaging by Using Lanthanide Nanoprobe with Enhanced Down-Shifting Emission beyond 1500 nm.

Visualization of tumor vessels/metastasis and cerebrovascular architecture is vitally important for analyzing pathological states of brain diseases and a tumor's abnormal blood vessels to improve cancer diagnoses. In vivo fluorescence imaging using second near-infrared emission beyond 1500 nm (NIR-IIb) has emerged as a next generation optical imaging method with significant improvement in imaging sensitivity and spatial resolution. Unfortunately, a highly biocompatible probe capable of generating NIR-IIb emission with sufficient brightness and uniformed size is still scarce. Here, we have proposed the poly(acrylic acid) (PAA)-modified NaLnF4:40Gd/20Yb/2Er nanorods (Ln = Y, Yb, Lu, PAA-Ln-NRs) with enhanced downshifting NIR-IIb emission, high quantum yield (QY), relatively narrow bandwidth (∼160 nm), and high biocompatibility via Ce3+ doping for high performance NIR-IIb bioimaging. The downshifting emission beyond 1500 nm is improved by 1.75-2.2 times with simultaneously suppressing the upconversion (UC) path in Y, Yb, and Lu hosts via Ce3+ doping. Moreover, compared with the traditionally used Y-based host, the QY of NIR-IIb emission in the Lu-based probe in water is improved from 2.2% to 3.6%. The explored bright NIR-IIb emitted PAA-Lu-NRs were used for high sensitivity small tumor (∼4 mm)/metastatic tiny tumor detection (∼3 mm), tumor vessel visualization with high spatial resolution (41 µm), and brain vessel imaging. Therefore, our findings open up the opportunity of utilizing the lanthanide based NIR-IIb probe with bright 1525 nm emission for in vivo optical-guided tumor vessel/metastasis and noninvasive brain vascular imaging.

Second near-infrared emissive lanthanide complex for fast renal-clearable in vivo optical bioimaging and tiny tumor detection.

In vivo optical imaging by using a new imaging window located at short-wavelength infrared region (1000-1700 nm, named as NIR II) presents an unprecedented improvement in imaging sensitivity and spatial resolution over the traditional visible and near-infrared light. However, the most developed NIR II-emitters are hardly excreted from live animals, leading to unknown long-term toxicity concerns, which hinder the widespread applications of this advanced imaging technology. Here, we developed a new generation molecular NIR II-emitting probe based on Nd-diethylene triamine pentacetate acid (DTPA) complex. The designed molecular Nd-DTPA probe with bright narrow band emission at 1330 nm is successfully used for highly sensitive in vivo NIR II bioimaging with rapid renal excretion, high biocompatibility and optical-guided tiny tumor (down to ∼3 mm) detection for the first time. Moreover, the Nd-DPTA complex also holds great promise as an X-ray contrast agent. These findings open up the possibility for designing a new generation of multi-modal small molecular probe for early tumor diagnosis and favor the clinic translation of the advanced NIR II imaging method.

Soft X-ray activated NaYF4:Gd/Tb scintillating nanorods for in vivo dual-modal X-ray/X-ray-induced optical bioimaging.

Lanthanide (Ln) nanocrystals using soft X-ray as an excitation source have received significant research interest due to the advantages of unlimited penetration depth of X-ray light. In this study, we demonstrated an efficient scintillator based on NaYF4:Gd nanorods (denoted as NRs) doped with different contents of terbium (Tb) ions for optical bioimaging under X-ray irradiation. The experimental results showed that the emission intensity was correlated to the doping contents of Tb3+, and the largest emission intensity was achieved by doping 15% Tb under excitation by soft X-ray light. In addition, the emission intensity of the as-prepared NRs can be significantly improved by increasing the excitation power and irradiation times of the X-ray. Owing to the efficient X-ray-induced emission, these NRs were successfully used as probes for X-ray-induced optical bioimaging with high sensitivity. In addition, the dual-modal X-ray imaging and X-ray induced optical bioimaging were performed on a mouse, which indicated that the NRs were promising dual-modal bioprobes. Therefore, the X-ray activation nature of the designed NRs makes them promising probes for biomedicine and X-ray-induced photodynamic therapy (PDT) applications owing to the unlimited penetration depth of X-ray excitation source and absence of autofluorescence.

M2+ Doping Induced Simultaneous Phase/Size Control and Remarkable Enhanced Upconversion Luminescence of NaLnF4 Probes for Optical-Guided Tiny Tumor Diagnosis.

Doping has played a vital role in constructing desirable hybrid materials with tunable functions and properties via incorporating atoms into host matrix. Herein, a simple strategy for simultaneously modifying the phase, size, and upconversion luminescence (UCL) properties of the NaLnF4 (Ln = Y, Yb) nanocrystals by high-temperature coprecipitation through nonequivalent M2+ doping (M = Mg2+ , Co2+ ) has been demonstrated. The phase transformation from cubic to hexagonal is readily achieved by doping M2+ . Compared with Mg-free sample, a remarkable enhancement of overall UCL (≈27.5 times) is obtained by doping Mg2+ . Interestingly, owing to the efficient UCL, red UCL-guided tiny tumor (down to 3 mm) diagnosis is demonstrated for the first time. The results open up a new way of designing high efficient UCL probe with combination of hexagonal phase and small size for tiny tumor detection.

Upconversion optical/magnetic resonance imaging-guided small tumor detection and in vivo tri-modal bioimaging based on high-performance luminescent nanorods.

In this work, we demonstrated multifunctional NaYbF4: Tm3+/Gd3+ upconversion (UC) nanorods (UCNRs) with near-infrared (NIR)-to-NIR emission and controlled phase and size for UC optical and T1/T2 dual-weighted magnetic resonance (MR) imaging-guided small tumor detection and tri-modal bioimaging. Cell toxicity and post-injection histology results revealed that our designed UCNRs present low biotoxicity and good biocompatibility in living animals. Real-time tracking based on UCNRs in living mice demonstrated that the UCNRs were mainly accumulated in the reticuloendothelial system (RES) and excreted through the hepatic pathway. Additionally, the UCNRs exhibited high X-ray absorption coefficient and large K-edge value, resulting in efficient in vivo CT imaging. A new type of binary (Yb3+/Gd3+) MR contrast agent for simultaneous T1/T2 dual-weighted MR imaging was achieved by doping Gd3+ into NaYbF4 host. Importantly, a small tumor (5 mm in diameter) could be detected in vivo by intravenously injecting UCNRs under UC optical and MR imaging modalities. Therefore, these multifunctional nanoprobes based on NaYbF4:Tm3+/Gd3+ UCNRs with remarkable NIR-to-NIR emission provide potential applications for tri-modal UC optical, CT, binary T1/T2 MR imaging, and early-stage tumor detection in nanomedicine.

A novel diarylheptanoid-bearing sesquiterpene moiety from the rhizomes of Alpinia officinarum.

A new diarylheptanoid analogue-bearing sesquiterpene moiety, named Alpinisin A, was isolated from the rhizomes of Alpinia officinarum Hance. The new structure was determined by various spectroscopic techniques (1)H-nuclear magnetic resonance ((1)H NMR), (13)C-attached proton test ((13)C-APT), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC), (1)H-(1)H correlation spectroscopy ((1)H-(1)HCOSY), nuclear overhauser effect spectroscopy (NOESY) and high resolution electrospray ionization mass spectrometry (HR-ESI-MS). The compound was tested for cytotoxic activity in vitro against human tumour cell lines (gastric carcinoma cell -7901 (SGC-7901), Michigan Cancer Foundation-7 (MCF-7) and Caski), which showed significant inhibitory effects with IC50 levels of 11.42, 15.14 and 14.78 µM, respectively. The novel chemical structure characterised with a diarylheptanoid linked to a chain-like sesquiterpenoid should be highlighted.