Research Progress on Chemical Constituents and Pharmacological Effects of Zexie (Alismatis Rhizoma)

Abstract

As a diuretic and dampness-eliminating medicinal agent in traditional Chinese medicine (TCM), Zexie (Alismatis Rhizoma) is commonly used for symptoms such as dysuria, edema and abdominal distension, diarrhea with oliguria, and dizziness due to phlegm–fluid retention. Systematic phytochemical studies have revealed that the active components of Zexie (Alismatis Rhizoma) are primarily triterpenoids, along with sesquiterpenes, polysaccharides, sterols, alkaloids, phenolic acids, and lignans. These components form the material basis for its pharmacological activities. Recent breakthroughs in pharmacological research have expanded beyond its traditionally recognized diuretic and anti-inflammatory effects: Its antiurolithiasis effect has been clearly linked to inhibiting the crystallization of stone components and promoting stone expulsion; its renal protective effect can ameliorate kidney injury by reducing oxidative stress and suppressing inflammatory responses in renal tissues; its lipid-lowering mechanism involves regulating lipid metabolism pathways and reducing lipid deposition; in terms of anticancer activity, it exhibits proliferation inhibition and apoptosis induction in various tumor cells such as liver, lung, and colon cancers; additionally, it shows significant antibacterial activity against pathogens, including Escherichia coli and Staphylococcus aureus.

Keywords

Alismatis Rhizoma - Zexie - chemical constituents - pharmacological effects - review

Introduction

Zexie (Alismatis Rhizoma), the dried tuber of Alisma plantago-aquatica or Alisma orientale in the genus Alisma, is cold in nature, sweet and bland in taste, and acts on the kidney and bladder meridians. With a history of thousands of years in China, it holds high medicinal value and abundant resource availability. First documented in Shennong's Classic of Materia Medica (Shen Nong Ben Cao Jing) as a top-grade herb, it has the effects of promoting diuresis, excreting dampness, clearing heat, resolving turbidity, and lowering lipids. It is included in several classical formulas such as Zexie Tang (Alisma Decoction) and Zhuling Tang (Polyporus Decoction), used to treat dysuria, edema, distension, and painful urinary dribbling due to heat.[1] Its cultivation in China is mainly concentrated in Sichuan, Fujian, and Jiangxi provinces, forming two mainstream commercial specifications, “Jian Zexie” and “Chuan Zexie,” based on regional differences, derived from A. plantago-aquatica and A. orientale, respectively—a classification explicitly included in the 2020 edition of the Chinese Pharmacopoeia.[2] [3] Zexie (Alismatis Rhizoma) is rich in chemical components, mainly including triterpenoids, sesquiterpenes, polysaccharides, sterols, alkaloids, phenolic acids, and lignans, among which triterpenoids are the primary pharmacologically active constituents. Guided by the traditional Chinese medicine (TCM) theory and based on its traditional efficacy, numerous studies have found that Zexie (Alismatis Rhizoma) and its extracts have significant effects in diuresis, antiurolithiasis, and lipid-lowering,[4] with some mechanisms preliminarily elucidated through research on signaling pathways (e.g., NF-κB, PI3K/Akt). Summarizing recent research progress on the chemical constituents and pharmacological effects of Zexie (Alismatis Rhizoma) provides a theoretical foundation for its rational clinical use and further development.

Chemical Constituents

Triterpenoids

Modern phytochemical studies indicate that the primary active constituents of Zexie (Alismatis Rhizoma) are triterpenoids, most of which possess a protostane-type tetracyclic triterpene skeleton and exhibit broad pharmacological activities.[5] Research on triterpenoids from Zexie (Alismatis Rhizoma) dates back to 1960, when Kamiya et al[6] first determined the complete stereochemical structure of alisol A using X-ray crystallography, specifically resolving the configuration at the ring junctions, thereby providing a standard reference for the structural classification and identification of such compounds. In China, research on the chemical component of triterpenoid from Zexie (Alismatis Rhizoma) began in 1996, when Cai et al[7] isolated two triterpenoids, Alisol B monoacetate and Alisol C monoacetate, from the plant. Mai et al[8] discovered structurally diverse novel protostane-type triterpenes from Zexie (Alismatis Rhizoma), including ten regular protostanes, one 29-norprotostane, and one 24-norprotostane, with the 29-norprotostane-type triterpene providing a novel lead compound for the structural optimization of human carboxylesterase 2 (hCE2) inhibitors. Ma et al[9] systematically clarified the structural lineages of terpenoids in Zexie (Alismatis Rhizoma), identifying multiple rare skeleton derivatives (e.g., endoperoxide-bridged triterpenes, norprotostanes), thereby enriching the natural triterpenoid compound library. Li[10] isolated 10 protostane-type triterpenes from a 70% ethanol extract of Zexie (Alismatis Rhizoma) and found that triterpenoids were primarily distributed in the liver, muscle, and kidney tissues of rats, indicating these organs and tissues are major sites of action and accumulation for the pharmacologically active substances of Zexie (Alismatis Rhizoma), providing a basis for its clinical use. Triterpenoids from Zexie (Alismatis Rhizoma) are listed in [Table 1] and shown in [Fig. 1].

Table 1 Triterpenoids from Zexie (Alismatis Rhizoma)

Number	Name	Reference	Source
1	Alisol A	[49]	a
2	Alisol A 23-acetate	[49]	a
3	Alisol A 24-acetate	[50]	a
4	11-deoxyalisol A	[50]	a
5	16-oxoalisol A	[50]	a
6	25-O-methylalisol A	[50]	a
7	25-O-ethylalisol A	[8] [9]	a
8	Alisol E	[51]	a
9	Alisol E 23-acetate	[51]	a
10	Alisol E 24-acetate	[52]	a
11	16β-methoxyalisol E	[53]	a
12	16β,25-dimethoxyalisol E	[54]	a
13	16β-hydroperoxyalisol E	[54]	a
14	Alisol H	[53] [55]	a
15	11,24-dihydlroxy-alsol H	[10]	a
16	Alisol T	[54]	a
17	11-deoxy-13β,17β-epoxyalisol A	[50]	a
18	13β,17β-epoxyalisol A	[50]	a
19	13β,17β-epoxyalisol A 24-acetate	[52]	a
20	11-deoxy-13β,17β-epoxyalisol B	[50] [55]	a
21	11-deoxy-13β,17β-epoxyalisol B 23-acetate	[50] [55]	a
22	13β,17β-epoxyalisol B	[50] [56]	a
23	Alisol D	[50] [57]	b
24	5β,29-dihydroxy alisol A	[58]	a
25	25-anhydroalisol A 11-acetate	[59]	a
26	25-anhydroalisol A 24-acetate	[59]	a
27	11-deoxy-25-anhydroalisol E	[8]	a
28	Alisol G	[51] [59]	a
29	Alisol G 23-acetate	[53]	a
30	Alisol X	[60]	a
31	3-oxo-16-oxo-11-anhydroalisol A	[8]	a
32	16-oxo-11-anhydroalisol A	[8] [10]	a
33	16-oxo-11-anhydroalisol A 24-acetate	[9]	a
34	Alismanol A	[8]	a
35	Alismanol C	[8]	a
36	15,16-dihydroalisol A	[8]	a
37	13β,17β-epoxy-24,25,26,27-tetranor-alisol A 23-oic acid	[9]	a
38	Alisol B	[49] [50]	a
39	Alisol B 23-acetate	[49] [50]	a
40	11-deoxyalisol B	[50]	a
41	11-deoxyalisol B 23-acetate	[50]	a
42	16β-acetoxy alisol B	[61]	a
43	16α-acetoxy alisol B	[61]	a
44	16β-hydroxy-alisol B 23-acetate	[49] [62]	a,b
45	16β-hydroperoxyalisol B	[54]	a
46	16β-hydroperoxyalisol B 23-acetate	[54]	a
47	16β-methoxyalisol B	[54]	a
48	16β-methoxyalisol B 23-acetate	[62]	b
49	Alisol C	[50]	a
50	Alisol C 23-acetate	[53]	a
51	11-deoxyalisol C	[57]	b
52	11-deoxyalisol C 23-acetate	[50]	a
53	20-hydroxyalisol C	[8]	a
54	Alisol F	[51]	a
55	Alisol F 24-acetate	[56]	a
56	25-methoxyalisol F	[54]	a
57	Alisol M 23-acetate	[55]	a
58	Alisol N 23-acetate	[55]	a
59	25-anhydro-alisol F	[9] [63]	a
60	16,23-oxidoalisol B	[49] [50]	a
61	Alisol I	[53] [55]	a
62	Alisol O	[64] [65]	a
63	24-deacetyl alisol O	[63] [65]	a
64	Alisol J 23-acetate	[55]	a
65	Alisol K 23-acetate	[55]	a
66	11,25-anhydro-alisol F	[66]	a
67	Alisol L 23-acetate	[55]	a
68	Alisol Q 23-acetate	[67]	a
69	Alisol S 23-acetate	[54]	a
70	3-oxo-11β,23-dihydroxy-24,24-dimethyl-26,27-dinorprotost-13(17)-en-25-oic acid	[68]	a
71	Alisol P	[68]	a
72	Alisol R	[54]	a
73	Alismaketone B 23-acetate	[69]	a
74	Alisolide	[68]	a
75	17-epi-alisolide A	[70]	a
76	Alismaketone A 23-acetate	[53]	a
77	Alismaketone C 23-acetate	[69]	a
78	Alisol U	[54]	a
79	Alisol V	[54]	a
80	Alismalactone 23-acetate	[53]	a
81	3-methylalismalactone 23-acetate	[69]	a
82	Alismanol D	[8]	a
83	24-epi alismanol D	[70]	a
84	Alismanol B	[8]	a
85	Alismanol E	[8]	a
86	Alismanol F	[8]	a
87	Alismanol G	[8]	a
88	Alismanol M	[71]	a
89	Alismanol O	[71]	a
90	Alismanol P	[71]	a
91	Alismanol Q	[71]	a
92	Neoalisol	[59]	a
93	Neoalisol 11,24-acetate	[59]	a
94	Alismanin A	[72]	a
95	Alismanin B	[72]	a
96	Alismanin C	[72]	a
97	Ursolic acid	[73]	a

^a Alisma plantago-aquatica.

^b Alisma orientale.

Fig. 1 Triterpenoids from Zexie (Alismatis Rhizoma).

Sesquiterpenoids

Sesquiterpenoids, along with triterpenoids, are major chemical constituents of Zexie (Alismatis Rhizoma), primarily featuring guaiane and eudesmane skeleton types. Research on sesquiterpenoids from Zexie (Alismatis Rhizoma) began in 1983 when Oshima et al[11] first isolated two sesquiterpenoids, 1β, 5β-guaia-6,10(15)-dien-4-ol and 4,10-epoxy-1β, 5β-guai-6-ene, from the plant. Liang et al[12] obtained nine sesquiterpenoids from Zexie (Alismatis Rhizoma): Orientalol L, orientalol M, orientalol N, orientalol O, orientalol P, alismanoid A, heyneanone D, leptocladol B, and chabrolidione B, and first reported the inhibitory effects of sesquiterpenoids on NO production in LPS-induced Caco-2 cells. Yu et al[13] first reported the presence of xanthane-type and salviolane-type sesquiterpenoids in the genus Alisma, significantly expanding the structural diversity of sesquiterpenoids within this genus and enriching the chemical profile of Alisma plants. To date, over 50 sesquiterpenoids have been isolated from Zexie (Alismatis Rhizoma). The names and structures of these compounds are listed in [Table 2] and shown in [Fig. 2].

Table 2 Sesquiterpenoids from Zexie (Alismatis Rhizoma)

Number	Name	Reference	Source
98	Alismoxide	[74] [75]	a,b
99	10-O-methyl-alismoxide	[50]	a
100	10-O-ethyl-alismoxide	[76]	a
101	Orientalol A	[74]	a
102	10-O-methyl-orientalol A	[76]	a
103	Orientalol B	[13] [74]	a,b
104	1αH,5αH-guaia-6-ene-4β,10β-diol	[9]	a
105	Alismanoid C	[77]	a
106	4α,10α-dihyroxy-5β-H-guaj-6-en	[78]	a
107	10α-hydroxy-4α-methoxy-guai-6-ene	[79]	a
108	4α,12-dihydroxyguaian-6,10-diene	[61]	a
109	4β,1,2-dihydroxyguaian-6,10-dien	[67] [73]	a
110	4-epi-alismoxide	[76]	a
111	11-hydroxy-8-ox-alismoxide	[61]	a
112	Alismorientols A	[80]	a
113	Alismorientols B	[80]	a
114	Alismol	[13] [74]	a,b
115	11-oxo-13-noralismol	[61] [76]	a
116	Ligucyperonol	[61]	a
117	Orientalol C	[74]	a
118	3β,4β-expoxy-chrysothol	[76]	a
119	Orientalol E	[75] [81]	a
120	Orientalol F	[75]	a
121	Orientalol G	[76]	a
122	Orientalol L	[82]	a
123	7α,10α-epoxy-salvialan-10β-ol	[13]	b
124	Orientalol N	[82]	a
125	Alismanoid B	[77]	a
126	Sulfoorientalols a	[83]	a
127	Sulfoorientalols b	[83]	a
128	Sulfoorientalols c	[83]	a
129	Sulfoorientalols d	[83]	a
130	Orientanone	[84]	a
131	Clovandiol	[78]	a
132	Germacrene C	[85]	a
133	Germacrene D	[85]	a
134	Gibberodione	[13]	b
135	Oplopanone	[13]	b
136	Entoplopanone	[9]	a
137	1β,11-dihydroxy-β-cyperone	[61]	a
138	1β-hydroxy-β-cyperone	[61]	a
139	Eudesma-4(14)-ene-1β,6a-diol	[50]	a
140	Orientalol O	[82]	a
141	Orientalol P	[82]	a
142	(10S)-11-hydroxy-β-cyperone	[79]	a
143	Zingibertriol	[79]	a
144	Alisguaiaone	[13]	a
145	(8R)-alismanoid A	[77]	a
146	(8S)-alismanoid A	[77]	a
147	Litseachromolaevane B	[79]	a
148	Orientalol M	[82]	a
149	Heyneanones D	[12]	a
150	Leptocladol B	[12]	a
151	Chabrolidione B	[12]	a

^a Alisma plantago-aquatica.

^b Alisma orientale.

Fig. 2 Sesquiterpenoids from Zexie (Alismatis Rhizoma).

Diterpenoids

Diterpenoids constitute a very minor fraction of the chemical constituents of Zexie (Alismatis Rhizoma), and few studies have been reported. Only four compounds, all of the kaurane-type tetracyclic diterpene class, have been documented. Their structures are listed in [Table 3] and shown in [Fig. 3].

Table 3 Diterpenoids from Zexie (Alismatis Rhizoma)

Number	Name	Reference	Source
152	Oriediterpenone	[86]	a
153	Oriediterpenonl	[86]	a
154	Oriediterpenonside	[86]	a
155	12-deoxyphorbol-13α-pentadecanoate	[58]	a

^a Alisma plantago-aquatica.

^b Alisma orientale.

Fig. 3 Diterpenoids from Zexie (Alismatis Rhizoma).

Other Constituents

Other constituents in Zexie (Alismatis Rhizoma) mainly include phenylpropanoids, phenolic acids, saccharides, and nitrogen-containing compounds. These compounds account for about one-third of the known compounds from Zexie (Alismatis Rhizoma), with phenylpropanoids and phenolic acids being chemical types isolated from the plant in recent years. These compounds are listed in [Table 4] and shown in [Fig. 4].

Table 4 Other constituents from Zexie (Alismatis Rhizoma)

Number	Name	Reference	Source
156	Uracil	[87]	a
157	Adenine	[87]	a
158	Uridine	[88]	a
159	Thymine	[89]	a
160	N-(3′-maleimidyl)-5-hydroxymethyl-2-pyrrole formaldehyde	[89]	a
161	Nicotinamide	[90]	a
162	4-pyrazin-2-yl-but-3-ene-1,2-diol	[90]	a
163	1H-indole-3-carboxylic acid	[78]	a
164	Indazole	[79]	a
165	Neoechinulin A	[79]	a
166	Magnolamide	[79]	a
167	Syringaresinol	[79]	a
168	Pinoresinol	[73]	a
169	Pinoresinol-4-O-β-D-glucoside	[79]	a
170	Isoeucommin A	[79]	a
171	(7,8-cis-8,8′-trans)-2,4-dihydroxy-3,5-dimethoxy-lariciresinol	[79]	a
172	1-(4-hydroxy-3-methoxy phenyl)-propane-1,2,3-triol	[79]	a
173	7-hydroxycoumarin	[73]	a
174	N-trans-feruloyl-N′-cis-feruloyl-cadaverine	[91]	a
175	N-trans-feruloyl-N′-cis-feruloyl-3-hydroxy-cadaverine	[91]	a
176	N,N′-trans-diferuloyl-3-oxo-cadaverine	[91]	a
177	N-trans-p-coumaroyl-N′-trans-feruloyl-3-hydroxy-cadaverine	[91]	a
178	Diferuloyl-cadaverine	[91]	a
179	N,N′-cis-diferuloyl-3-hydroxy-cadaverine	[91]	a
180	N,N′-diferuloyl-putrescine	[91]	a
181	(E,Z)-terrestribisamide	[91]	a
182	(Z,Z)-terrestribisamide	[91]	a
183	Alisman SI	[92]	a
184	Alisman PII	[93]	a
185	Manninotriose	[94]	a
186	Verbascotetraose	[94]	a
187	Verbascose	[73] [94]	a
188	Raffinose	[94]	a
189	Stachyose	[94]	a
190	Saccharose	[94]	a
191	β-D-fructofuranose	[94]	a
192	5-hydroxymethylfuraldehyde	[94]	a
193	α-D-fructofuranose	[94]	a
194	Ethyl α-D-fructofuranoside	[94]	a
195	Ethyl β-D-fructofuranoside	[94]	a
196	β-sitosterol	[7] [88]	a
197	β-sitosterol-3-O-6-stearyl glucoside	[95]	b
198	β-sitosterol-3-O-6-stearate	[7]	a
199	Ergosta-6,22-diene-3β,5α,8α-triol	[73]	a
200	Daucosterol-6′-O-stearate	[7] [88]	a
201	Daucosterol	[88]	a
202	Amentoflavone	[66]	a
203	Robustaflavone	[66]	a
204	2,2′,4-trihydroxychalcone	[66]	a
205	7,4′-dihydroxyisoflavone	[73]	a
206	Calycosin	[73]	a
207	Luteolin	[73]	a
208	Apigenin	[73]	a
209	Plantain A	[96]	a
210	Ferulic acid	[96]	b
211	Rynchopeterine A	[96]	b
212	Rynchopeterine B	[96]	b
213	Rosmarinic acid	[96]	b
214	p-hydroxy benzaldehyde	[73]	a
215	(Z)-8,11,12-trihydroxyoctadec-9-enoic acid	[89]	a
216	2′,3′-dihydroxy propylentade canoate	[89]	a
217	Butanedioic acid	[78] [87]	a
218	Palmitin	[90]	a
219	1-monolinolein	[90]	a
220	n-tricosane	[7]	a
221	Ethyl octadecanoate	[73]	a
222	Methyl palmitate	[73]	a
223	1-behenyl alcohol	[88]	a
224	Dulcitol	[88]	a
225	Stearic acid	[7] [73]	a
226	1-glyceryl stearate	[7]	a
227	Rheum emodin	[7]	a

^a Alisma plantago-aquatica.

^b Alisma orientale.

Fig. 4 Other constituents from Zexie (Alismatis Rhizoma).

Pharmacological Effects

Studies have shown that crude extracts and monomeric compounds from Zexie (Alismatis Rhizoma) possess various pharmacological effects, including diuretic, antiurolithiasis, renal protective, hypoglycemic, hypolipidemic, and anti-inflammatory activities, as well as the ability to activate the Farnesoid X receptor and inhibit carboxylesterases. Among these, its diuretic, antiurolithiasis, and hypolipidemic effects have been more intensively studied.[14]

Diuretic Effect

Zexie (Alismatis Rhizoma) has the effect of promoting diuresis and excreting dampness, and its diuretic activity has been relatively well-studied. Tao et al[15] established a reliable UHPLC-MS/MS analytical method to track active components in Chinese medicinal and used this method to identify three diuretic components from Zexie (Alismatis Rhizoma): Alisol A, alisol B, and alisol F. Zhang et al[16] evaluated the diuretic effect of total triterpenoids from Zexie (Alismatis Rhizoma) and found that they significantly increased urine volume and promoted electrolyte excretion in saline-loaded rats. Furthermore, alisol A, 24-acetylalisol A, alisol B, 23-acetylalisol B, and 23-acetylalisol C shared the same diuretic mechanism as the total triterpenoids, suggesting that triterpenoids could be developed as potential diuretic agents. Additionally, studies indicate that a 95% ethanol extract of Zexie (Alismatis Rhizoma) has a dual effect on rat kidney function, acting as a diuretic at low doses and exhibiting an antidiuretic effect at high doses.[17]

An aqueous extract of Zexie (Alismatis Rhizoma) can significantly reduce AQP2 mRNA expression in the rat renal medulla, thereby increasing urine volume.[18] In clinical studies, the aqueous extract of Zexie (Alismatis Rhizoma) significantly increased urine output in patients with cirrhotic portal hypertension, a mechanism potentially related to the Na⁺–Cl⁻ cotransporter in the distal renal vasculature.[19] [20]

Antiurolithiasis and Renal Protective Effects

Qu et al[21] found that the total triterpenoid extract of Zexie (Alismatis Rhizoma) reversed changes in serum urea nitrogen, creatinine, and urinary calcium in rats with ethylene glycol and alfacalcidol-induced urinary calcium oxalate stones. It also reduced the number and size of deposited calcium oxalate crystals, protecting the kidney from severe damage, further indicating that total triterpenoids are the active components responsible for the antiurolithiasis effect of Zexie (Alismatis Rhizoma). Cao et al[22] discovered that active components of Zexie (Alismatis Rhizoma) could inhibit renal stone formation by downregulating the expression of bikunin mRNA in rat kidneys, thereby reducing calcium oxalate formation. A 50% methanol extract of Zexie (Alismatis Rhizoma) significantly reduced calcium ion content in rat renal tissue, demonstrating significant antiurolithiasis activity.[23] The ethyl acetate eluate of an ethyl acetate extract of Zexie (Alismatis Rhizoma) exerted antiurolithiasis effects by reducing calcium oxalate crystal deposition in renal tissue and the expression of IαI in renal tubular epithelial cells.[24] Furthermore, a 95% ethanol extract of Zexie (Alismatis Rhizoma) protected mouse kidney by improving the activity of renal antioxidant enzymes and inhibiting lipid peroxidation.[25] Studies have shown that an aqueous extract of Zexie (Alismatis Rhizoma) also significantly inhibits the growth and aggregation of calcium oxalate, thereby inhibiting renal stone formation.[26] [27] Cao et al[28] found that Zexie (Alismatis Rhizoma) assists in stone expulsion through a triple mechanism involving diuresis, crystallization inhibition, and anti-inflammatory action, supported by substantial clinical evidence and a high safety profile. Its effective components are primarily triterpenoids, and its efficacy can be further enhanced when combined with Jinqiancao (Lysimachiae Herba) or potassium citrate.

Hypolipidemic Effect

Zexie (Alismatis Rhizoma) has the effect of resolving turbidity and lowering lipids, and is commonly used clinically to treat fatty liver disease and hyperlipidemia. Miao et al found that Zexie (Alismatis Rhizoma) ameliorated disorders of amino acid, purine, pyrimidine, and energy metabolism induced by a high-fat diet, and identified 19 biomarkers related to hyperlipidemia and antihyperlipidemia effects.[29] Dan et al found that Zexie (Alismatis Rhizoma) significantly reduced levels of ALT, AST, hepatic cholesterol, triglycerides, and HDL-cholesterol, and identified 23-acetylalisol B and 24-acetylalisol A as the main active components responsible for its hypolipidemic effects.[30] Studies have shown that 24-acetylalisol A exerts hypolipidemic effects by inhibiting HMG-CoA reductase activity, thereby reducing total cholesterol, LDL-cholesterol, and triglyceride levels in hyperlipidemic mice.[31] An ethanol extract of Zexie (Alismatis Rhizoma) can reduce acetyl-CoA, a substrate for cholesterol synthesis, and decrease hepatic lipid accumulation.[32] [33] Studies have shown that a water decoction of Zexie (Alismatis Rhizoma) improves hepatic lipid deposition and reduces palmitic acid-induced steatosis and injury in HepG2 cells modeling non-alcoholic fatty liver disease.[34]

Hepatoprotective Effects

An ethanol extract of Zexie (Alismatis Rhizoma) can effectively regulate disorders of blood lipid metabolism, inhibit hepatic lipid deposition, promote liver regeneration in partially hepatectomized mice, and alleviate carbon tetrachloride-induced hepatotoxicity in mice.[35] [36] [37] Furthermore, polysaccharides from Zexie (Alismatis Rhizoma) also exhibit a certain protective effect against carbon tetrachloride-induced acute liver injury in mice.[38] Luan et al[39] found that (23S)-11β, 23-dihydroxy-8α, 9β, 14β-dammar-13(17)-ene-3, 24-dione from Zexie (Alismatis Rhizoma) modulated the mRNA expression levels of FXR, UGT2B4, BSEP, SHP1, and FXR downstream proteins, thereby exerting a protective effect against non-alcoholic fatty liver disease. Using luciferase reporter assays, siRNA experiments, and further molecular docking studies, Meng et al demonstrated that 23-acetylalisol B protects against cholestasis and anti-inflammatory drug-induced hepatotoxicity by activating farnesoid X receptor (FXR).[40] [41]

Anti-Inflammatory Effects

Modern pharmacological studies indicate that conditions such as hyperlipidemia, hypertension, and hyperglycemia are closely related to inflammatory factors.[42] Network pharmacology research by some scholars suggests that Zexie (Alismatis Rhizoma) may exert its anti-inflammatory effects by modulating the PI3K-AKT and ErbB signaling pathways.[43] Liang et al isolated eight protostane-type triterpenoids from Zexie (Alismatis Rhizoma), all of which significantly inhibited NO production in LPS-induced Caco-2 cells, with alisol A 23-acetate and alisol G showing the strongest inhibitory activity.[37] Additionally, studies show that Zexie Tang (Alisma Decoction) and total triterpenoids from Zexie (Alismatis Rhizoma) exert anti-inflammatory effects by downregulating the mRNA expression of inflammatory mediators such as IL-1β and IL-6.[44] [45]

Other Pharmacological Effects

Studies indicate that the monomeric compound 23-acetylalisol B from Zexie (Alismatis Rhizoma) exerts anticancer effects by inducing apoptosis and autophagy in A549 and NCI-H292 cells.[46] Triterpenoids from Zexie (Alismatis Rhizoma) exhibit inhibitory effects against Enterococcus faecium and Pseudomonas aeruginosa, and both triterpenoids and sesquiterpenoids from Zexie (Alismatis Rhizoma) can inhibit Bacillus subtilis and Staphylococcus aureus.[42] An ethanol extract of Zexie (Alismatis Rhizoma) can inhibit α-glucosidase activity, while an aqueous extract can inhibit intestinal glucose absorption and accelerate gluconeogenesis, thereby exerting hypoglycemic effects.[4] Zhu et al found that triterpenoids such as alisol C and alisol L in the aqueous extract of Zexie (Alismatis Rhizoma) possess hypoglycemic activity, potentially related to the activation of Nrf2 gene expression.[47] Investigation of Zexie (Alismatis Rhizoma) residue (dregs) revealed a high content of 23-acetylalisol B, and the concentration of its ethanol extract showed a positive correlation with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging activities, indicating that the residue possesses good antioxidant activity.[48]

Conclusion

Zexie (Alismatis Rhizoma), used in TCM clinical practice as a diuretic and dampness-eliminating medicinal, is commonly indicated for dysuria, edema and distension, diarrhea with oliguria, and dizziness due to phlegm–fluid retention. Systematic phytochemical studies reveal that Zexie (Alismatis Rhizoma) is rich in various structural types of constituents, including triterpenoids, sesquiterpenoids, polysaccharides, sterols, alkaloids, phenolic acids, and lignans. Research has identified protostane-type tetracyclic triterpenoids and polysaccharides as its core active components and established a “component–target–pharmacological effect” correlation framework: Triterpenoids primarily mediate diuretic, hepatorenal protective, and anti-inflammatory effects, while polysaccharides primarily contribute to hypolipidemic effects and improvement of insulin resistance, fully corroborating its traditional efficacy of “promoting diuresis and excreting dampness.” Although progress has been made, current pharmacological research on Zexie (Alismatis Rhizoma) often focuses on crude extracts, with fewer studies on the pharmacological activities of monomeric chemical constituents. Furthermore, research on A. orientale remains relatively limited. Future efforts should strengthen the study of the chemical constituents of A. orientale to provide a reference for the material basis, processing methods, and quality evaluation of Zexie (Alismatis Rhizoma).

Conflict of Interest

The authors declare no conflict of interest.

CRediT Authorship Contribution Statement

Wanbing Shang: Investigation and writing—original draft. Haoyue Yuan: Investigation. Linlin Li: Investigation. Bian Wang: Conceptualization, writing-review & editing, and funding acquisition.

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Publication History

Received: 29 July 2025

Accepted: 22 September 2025

Article published online:
30 December 2025