Researchers at Jinan University and the Chinese Academy of Sciences, Shenzhen, reported on the discovery of a new category of phthalide compound in female ginseng (Angelica sinensis), one of which exhibited potent anti-osteoporotic activity in cell-based lab tests. The team also devised a method for synthesizing the compound—which they called falcarinphthalide A—in the lab at sufficient quantities to support in vitro testing.

暨南大学和深圳中国科学院的研究人员报道了在女参（当归）中发现的一类新的邻苯二甲酰化合物，其中一种在基于细胞的实验室测试中表现出有效的抗骨质疏松活性。该团队还设计了一种合成该化合物的方法，该化合物在实验室中被称为falcarinthalidate a，其量足以支持体外测试。

Their results showed that the compound exhibits a distinctive structure and mechanism that sets it apart from existing drugs used to treat osteoporosis. Tests found that the compound’s potent antiosteoporotic activity was linked with its ability to inhibit NF-κB and c-Fos signaling-mediated osteoclastogenesis..

他们的研究结果表明，该化合物具有独特的结构和机制，使其与用于治疗骨质疏松症的现有药物不同。测试发现，该化合物有效的抗骨质疏松活性与其抑制NF-κB和c-Fos信号传导介导的破骨细胞生成的能力有关。。

Hao Gao, PhD, at Jinan University Institute of Traditional Chinese Medicine and Natural Products, and Xin-Luan Wang, PhD, at the Chinese Academy of Sciences Translational Medicine R&D Center, and colleagues suggest their discoveries could point to new possibilities for developing osteoporosis treatments that are based on the female ginseng compound, whether in its current form or used as a structural template for further drug development..

暨南大学中医药与天然产物研究所的郝高博士和中国科学院转化医学研发中心的王新銮博士及其同事认为，他们的发现可能为开发基于女参化合物的骨质疏松症治疗方法提供新的可能性，无论是目前的形式还是用作进一步药物开发的结构模板。。

The team reported on its study in ACS Central Science, in a paper titled, “Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from Angelica sinensis and its Bioinspired Total Synthesis,” in which they concluded, “The discovery of falcarinphthalide A (1) offers a groundbreaking molecular framework for potential therapeutic interventions targeting osteoporosis and other metabolic bone disorders.”.

该团队在ACS Central Science上发表了一篇题为“从当归中发现一种有效的抗骨质疏松药物分子支架及其生物启发的全合成”的论文，报告中总结道，“发现了镰刀菌素a（1）为针对骨质疏松症和其他代谢性骨疾病的潜在治疗干预提供了开创性的分子框架。”。

Osteoporosis is “a systemic metabolic bone disease characterized by loss of bone mass and strength, leading to increased bone fragility and susceptibility,” the authors explained, citing figures indicating that in the United States osteoporosis and low bone mass impact 54 million adults over the age of 50 years.

作者解释说，骨质疏松症是“一种全身性代谢性骨病，其特征是骨量和强度下降，导致骨脆性和易感性增加”，引用的数字表明，在美国，骨质疏松症和低骨量会影响5400万50岁以上的成年人。

The disorder can progress to significant disability, such as hip and spine fractures, and financial burdens, such as lost wages and hospitalization. “The high incidence, rate of disability, and economic burden of osteoporosis have rendered it as a major global public health concern, drawing the attention of the World Health Organization,” the investigators continued..

这种疾病可以发展为严重的残疾，如髋部和脊柱骨折，以及经济负担，如工资损失和住院治疗。研究人员继续说道：“骨质疏松症的高发病率、致残率和经济负担使其成为全球主要的公共卫生问题，引起了世界卫生组织的关注。”。。

Several drugs have proven effective in either preventing bone loss or promoting bone formation, but each comes with potential side effects, including injury to jaw and leg bones. “The current available first-line drugs for osteoporosis include bisphosphonates, hormone, and antibody-based drugs,” the authors further noted.

事实证明，几种药物在预防骨质流失或促进骨骼形成方面都是有效的，但每种药物都有潜在的副作用，包括对颌骨和腿骨的损伤。作者进一步指出：“目前可用于治疗骨质疏松症的一线药物包括双膦酸盐、激素和基于抗体的药物。”。

“Although these drugs have specific clinical efficacy for osteoporosis, their side effects, long-term safety, and high cost cannot be ignored.”.

“尽管这些药物对骨质疏松症具有特定的临床疗效，但其副作用，长期安全性和高成本不容忽视。”。

Searching for alternative treatments, the researchers turned to female ginseng, which has long been used in traditional Chinese medicine (TCM) to treat osteoporosis. “Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis,” the authors further wrote..

为了寻找替代疗法，研究人员转向了长期用于中医治疗骨质疏松症的女参。作者进一步写道：“当归（Angelica sinensis）在欧美俗称东魁，在中国俗称当归，是一种广泛用于预防和治疗骨质疏松症的药用植物。”。。

For their study, the team performed chemical extraction on female ginseng, and identified two new compounds, calling them falcarinphthalide A and B, that were structurally unlike anything previously discovered in the plant. “We report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4),” they wrote.

在他们的研究中，该团队对雌性人参进行了化学提取，并鉴定出两种新化合物，称为镰刀菌素A和B，它们在结构上与先前在植物中发现的任何化合物都不同。他们写道：“我们报道了从当归中发现的一类新的邻苯二甲酰胺，即镰刀菌素a和B（1和2），其中包含两个片段，（3R，8S）-镰刀菌素二醇（3）和（Z）-藁本内酯（4）。”。

“This discovery reveals an entirely new subclass of TCM chemical constituent, and these two compounds represent a new category of phthalide in natural products.”.

“这一发现揭示了中药化学成分的一个全新亚类，这两种化合物代表了天然产物中一类新的邻苯二甲酰。”。

The investigators then determined potential biosynthetic precursors and metabolic pathways that the plants use to form these compounds. Then, with these mechanisms as starting points, the team devised lab synthesis methods and produced the compounds at quantities sufficient for biological testing. Inspired by the traditional efficacy of female ginseng, the team tested the compounds for their impact on the formation of cells called osteoclasts, which facilitate bone loss..

然后，研究人员确定了植物用于形成这些化合物的潜在生物合成前体和代谢途径。然后，以这些机制为出发点，该团队设计了实验室合成方法，并生产出足以进行生物测试的化合物。受女参传统功效的启发，该团队测试了这些化合物对破骨细胞形成的影响，破骨细胞可促进骨质流失。。

They observed that only falcarinphthalide A and its precursors showed osteoclast inhibitory activity and an anti-osteoporotic effect. “The bioassays revealed that falcarinphthalide A (1) and its biosynthetic precursors (3 and 4) displayed potent antiosteoclastogenic activities, whereas falcarinphthalide B (2) was inactive,” they wrote.

他们观察到，只有镰刀菌素A及其前体显示出破骨细胞抑制活性和抗骨质疏松作用。他们写道：“生物测定显示，镰刀菌素A（1）及其生物合成前体（3和4）显示出有效的抗破骨细胞生成活性，而镰刀菌素B（2）则无活性。”。

Further analysis showed that falcarinphthalide A blocked key molecular pathways involved in osteoclast generation. “Significantly, falcarinphthalide A (1) exerts a multifaceted mechanism of action by inhibiting RANKL-induced osteoclastogenesis through the suppression of both the NF-κB and c-Fos pathways.”.

进一步的分析表明，镰刀菌素A阻断了破骨细胞生成的关键分子途径。“值得注意的是，falcarinphthalide A（1）通过抑制NF-κB和c-Fos途径来抑制RANKL诱导的破骨细胞生成，从而发挥多方面的作用机制。”。

The team suggests that falcarinphthalide A exhibits a distinctive structure and mechanism that sets it apart from existing drugs such as bisphosphonates and estrogens. “These distinguishing features hold great potential for overcoming the adverse side effects commonly associated with current medications,” they wrote.

该团队认为，镰刀菌素A具有独特的结构和机制，使其与现有药物如双膦酸盐和雌激素区别开来。他们写道：“这些独特的特征具有克服目前药物常见的不良副作用的巨大潜力。”。

Acknowledging that more research will be needed to identify the compound’s target receptors, study its in vivo efficacy, and look at potential structural modifications, the team nevertheless concluded, “Overall, these ground-breaking findings not only extend the natural product skeleton categories but also highlight the potential of natural products as a source of novel molecular scaffold for treating osteoporosis.”.

该团队承认需要更多的研究来鉴定该化合物的靶受体，研究其体内功效，并研究潜在的结构修饰，但得出结论，“总的来说，这些突破性的发现不仅扩展了天然产物的骨架类别，而且突出了天然产物作为治疗骨质疏松症的新型分子支架来源的潜力。”。

Drug development (Pharmacology)Health care organizationsHerbal medicineOsteoporosisTraditional Chinese medicine

药物开发（药理学）保健机构Sherbal medicine骨质疏松症传统中药