文献类型：期刊文献

英文题名：From Pharmacological Uncertainty to Inhalation Development: An Evidence-Gated Roadmap for Codonopsis-Derived Triterpenoid Saponins

作者：Zhang, Xiaohua[1];Yang, Chunxia[1];Wang, Ping[2];Yang, Ping[2];Liu, Shanru[3,4];Liu, Shubin[1,2,4];Yang, Xiaoling[5]

第一作者：Zhang, Xiaohua

通信作者：Liu, SB[1]

机构：[1]Gansu Prov Hosp Tradit Chinese Med, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China;[2]Lanzhou Univ Technol, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China;[3]Chinese Acad Agr Sci, Lanzhou Inst Husb & Pharmaceut Sci, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China;[4]Gansu Prov Key Lab Qual & Stand Res Tradit Chinese, Dept Pharm, Lanzhou 730101, Gansu, Peoples R China;[5]Gansu Univ Chinese Med, Affiliated Hosp, Dept Pharm, Lanzhou 730020, Gansu, Peoples R China

第一机构：Gansu Prov Hosp Tradit Chinese Med, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp Tradit Chinese Med, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China.

年份：2026

卷号：20

起止页码：647578

外文期刊名：DRUG DESIGN DEVELOPMENT AND THERAPY

收录：;Scopus(收录号：2-s2.0-105052427484);WOS:【SCI-EXPANDED(收录号:WOS:001888889200001)】；

基金：This work was supported by the Gansu Provincial Natural Science Foundation (Nos. 25JRRA262 and 25JRRA260) ; the Lanzhou Science and Technology Development Guidance Plan (No. 2023-ZD-44) ; the Gansu Provincial Young Talent Project (No. 2026QNGR045) ; and the Open Fund of the Gansu Provincial Key Laboratory of Quality and Standard Research of Traditional Chinese Medicine (No. ZYZL2025-07) .

语种：英文

外文关键词：Codonopsis lanceolata; lancemaside A; echinocystic acid; triterpenoid saponins; pulmonary drug delivery; inhalation

摘要：Codonopsis-derived triterpenoid saponins merit investigation because preclinical studies identify immunomodulatory activity and a biologically active parent-metabolite relationship. Pulmonary delivery could increase exposure at a lung target while limiting unnecessary systemic exposure, but uncertain immune direction, membrane interactions, pulmonary absorption, and repeated-dose safety prevent a direct formulation recommendation. This critical narrative review evaluates chemical identity, lung pharmacology, and transferable delivery precedents using targeted searches updated through September 16, 2026 and a structured assessment of study relevance and limitations. Evidence is distinguished by material and route: defined saponins or fractions, composition-characterized botanical extracts, the associated metabolite echinocystic acid, and unrelated engineering precedents. Earlier antiinflammatory lancemaside A studies and a 2026 immunostimulatory study in interferon-gamma-primed macrophages require matched replication rather than a claim of an established biphasic mechanism. Oral C. lanceolata extract efficacy in allergic lung inflammation and echinocystic acid pharmacology support further investigation but do not validate an inhaled parent saponin. No qualifying therapeutic aerosol-inhalation study of a Codonopsis saponin, standardized saponin fraction, or composition-characterized extract was identified in the searches performed. We propose four connected development stages: select a reproducibly beneficial active entity; establish pulmonary safety and local pharmacokinetics/pharmacodynamics with the simplest feasible formulation; correct a demonstrated delivery limitation when necessary; and integrate efficacy, device-patient suitability, storage stability, and manufacturing. Lipid carriers, spray-dried or spray-freeze-dried powders, mucus-modifying surfaces, and targeting systems are assessed against their measured benefits and failure modes. Numerical targets remain explicit development hypotheses rather than regulatory standards. The framework supports local pulmonary treatment as the initial objective and makes progression, reformulation, and termination conditional on evidence. Plain Language Summary: Some compounds in Codonopsis plants can change inflammatory and immune responses in laboratory studies. Delivering a useful compound to the lungs might help it reach diseased tissue while reducing exposure elsewhere in the body. However, this benefit has not been demonstrated for an inhaled Codonopsis saponin, and increasing lung exposure could also increase irritation or unwanted immune activity. We examined what existing studies can and cannot tell us about this approach. The plant extract, a purified saponin, and a metabolite formed after oral treatment must be evaluated separately. Different laboratory studies have also reported opposite immune effects for lancemaside A. Our roadmap therefore begins by identifying the active material and checking that its effects are helpful under conditions relevant to the intended lung disease. The next step measures safety and local drug exposure using a simple inhaled formulation. More complex carriers or coatings are considered only when measurements identify a problem they could solve. The final stage brings together treatment effects, storage, manufacturing, the inhaler, and the patient's ability to use it. This approach aims to identify useful candidates and stop unsuitable ones before more elaborate development.